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Single-cell NAD(H) levels predict clonal lymphocyte expansion dynamics Sci. Immunol (IF 24.8) Pub Date : 2024-03-15 Lucien Turner, Tran Ngoc Van Le, Eric Cross, Clemence Queriault, Montana Knight, Krittin Trihemasava, James Davis, Patrick Schaefer, Janet Nguyen, Jimmy Xu, Brian Goldspiel, Elise Hall, Kelly Rome, Michael Scaglione, Joel Eggert, Byron Au-Yeung, Douglas C. Wallace, Clementina Mesaros, Joseph A. Baur, Will Bailis
Adaptive immunity requires the expansion of high-affinity lymphocytes from a heterogeneous pool. Whereas current models explain this through signal transduction, we hypothesized that antigen affinity tunes discrete metabolic pathways to license clonal lymphocyte dynamics. Here, we identify nicotinamide adenine dinucleotide (NAD) biosynthesis as a biochemical hub for the T cell receptor affinity–dependent
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A metabolic pacer ensures smooth running of the lymphocyte activation race Sci. Immunol (IF 24.8) Pub Date : 2024-03-15 Veera Panova, Arianne C. Richard
Upon lymphocyte stimulation, accumulation of intracellular NAD(H) reflects the strength of antigen receptor signals and controls the rate of cell cycle entry and proliferation (see related Research Article by Turner et al.).
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Gut bacteria–derived serotonin promotes immune tolerance in early life Sci. Immunol (IF 24.8) Pub Date : 2024-03-15 Katherine Z. Sanidad, Stephanie L. Rager, Hannah C. Carrow, Aparna Ananthanarayanan, Ryann Callaghan, Lucy R. Hart, Tingting Li, Purnima Ravisankar, Julia A. Brown, Mohammed Amir, Jenny C. Jin, Alexandria Rose Savage, Ryan Luo, Florencia Mardorsky Rowdo, M. Laura Martin, Randi B. Silver, Chun-Jun Guo, Jan Krumsiek, Naohiro Inohara, Melody Y. Zeng
The gut microbiota promotes immune system development in early life, but the interactions between the gut metabolome and immune cells in the neonatal gut remain largely undefined. Here, we demonstrate that the neonatal gut is uniquely enriched with neurotransmitters, including serotonin, and that specific gut bacteria directly produce serotonin while down-regulating monoamine oxidase A to limit serotonin
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A metabolic pacer ensures smooth running of the lymphocyte activation race Sci. Immunol (IF 24.8) Pub Date : 2024-03-15 Veera Panova, Arianne C. Richard
Upon lymphocyte stimulation, accumulation of intracellular NAD(H) reflects the strength of antigen receptor signals and controls the rate of cell cycle entry and proliferation (see related Research Article by Turner et al .).
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RORγt up-regulates RAG gene expression in DP thymocytes to expand the Tcra repertoire Sci. Immunol (IF 24.8) Pub Date : 2024-03-15 Abani Kanta Naik, Danielle J. Dauphars, Elizabeth Corbett, Lunden Simpson, David G. Schatz, Michael S. Krangel
Recombination activating gene (RAG) expression increases as thymocytes transition from the CD4 − CD8 − double-negative (DN) to the CD4 + CD8 + double-positive (DP) stage, but the physiological importance and mechanism of transcriptional up-regulation are unknown. Here, we show that a DP-specific component of the recombination activating genes antisilencer (DPASE) provokes elevated RAG expression in
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Single-cell NAD(H) levels predict clonal lymphocyte expansion dynamics Sci. Immunol (IF 24.8) Pub Date : 2024-03-15 Lucien Turner, Tran Ngoc Van Le, Eric Cross, Clemence Queriault, Montana Knight, Krittin Trihemasava, James Davis, Patrick Schaefer, Janet Nguyen, Jimmy Xu, Brian Goldspiel, Elise Hall, Kelly Rome, Michael Scaglione, Joel Eggert, Byron Au-Yeung, Douglas C. Wallace, Clementina Mesaros, Joseph A. Baur, Will Bailis
Adaptive immunity requires the expansion of high-affinity lymphocytes from a heterogeneous pool. Whereas current models explain this through signal transduction, we hypothesized that antigen affinity tunes discrete metabolic pathways to license clonal lymphocyte dynamics. Here, we identify nicotinamide adenine dinucleotide (NAD) biosynthesis as a biochemical hub for the T cell receptor affinity–dependent
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Transmembrane domain–driven PD-1 dimers mediate T cell inhibition Sci. Immunol (IF 24.8) Pub Date : 2024-03-08 Elliot A. Philips, Jia Liu, Audun Kvalvaag, Alexander M. Mørch, Anna S. Tocheva, Charles Ng, Hong Liang, Ian M. Ahearn, Ruimin Pan, Christina C. Luo, Alexander Leithner, Zhihua Qin, Yong Zhou, Antonio Garcia-España, Adam Mor, Dan R. Littman, Michael L. Dustin, Jun Wang, Xiang-Peng Kong
Programmed cell death-1 (PD-1) is a potent immune checkpoint receptor on T lymphocytes. Upon engagement by its ligands, PD-L1 or PD-L2, PD-1 inhibits T cell activation and can promote immune tolerance. Antagonism of PD-1 signaling has proven effective in cancer immunotherapy, and conversely, agonists of the receptor may have a role in treating autoimmune disease. Some immune receptors function as dimers
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Subcapsular sinus macrophages maximize germinal center development in non-draining lymph nodes during blood-borne viral infection Sci. Immunol (IF 24.8) Pub Date : 2024-03-08 Cynthia C. Aguilar, Anurag Kalia, Morgan E. Brisse, Kimberly A. Dowd, Olivia Wise-Dent, Katherine E. Burgomaster, Joanna Droppo, Theodore C. Pierson, Heather D. Hickman
Lymph node (LN) germinal centers (GCs) are critical sites for B cell activation and differentiation. GCs develop after specialized CD169+ macrophages residing in LN sinuses filter antigens (Ags) from the lymph and relay these Ags into proximal B cell follicles. Many viruses, however, first reach LNs through the blood during viremia (virus in the blood), rather than through lymph drainage from infected
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Beyond T cell exhaustion: TIM-3 regulation of myeloid cells Sci. Immunol (IF 24.8) Pub Date : 2024-03-08 Karen O. Dixon, Gonzalo Fernandez Lahore, Vijay K. Kuchroo
T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) is an important immune checkpoint molecule initially identified as a marker of IFN-γ–producing CD4 + and CD8 + T cells. Since then, our understanding of its role in immune responses has significantly expanded. Here, we review emerging evidence demonstrating unexpected roles for TIM-3 as a key regulator of myeloid cell function, in
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Subcapsular sinus macrophages maximize germinal center development in non-draining lymph nodes during blood-borne viral infection Sci. Immunol (IF 24.8) Pub Date : 2024-03-08 Cynthia C. Aguilar, Anurag Kalia, Morgan E. Brisse, Kimberly A. Dowd, Olivia Wise-Dent, Katherine E. Burgomaster, Joanna Droppo, Theodore C. Pierson, Heather D. Hickman
Lymph node (LN) germinal centers (GCs) are critical sites for B cell activation and differentiation. GCs develop after specialized CD169 + macrophages residing in LN sinuses filter antigens (Ags) from the lymph and relay these Ags into proximal B cell follicles. Many viruses, however, first reach LNs through the blood during viremia (virus in the blood), rather than through lymph drainage from infected
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Transmembrane domain–driven PD-1 dimers mediate T cell inhibition Sci. Immunol (IF 24.8) Pub Date : 2024-03-08 Elliot A. Philips, Jia Liu, Audun Kvalvaag, Alexander M. Mørch, Anna S. Tocheva, Charles Ng, Hong Liang, Ian M. Ahearn, Ruimin Pan, Christina C. Luo, Alexander Leithner, Zhihua Qin, Yong Zhou, Antonio Garcia-España, Adam Mor, Dan R. Littman, Michael L. Dustin, Jun Wang, Xiang-Peng Kong
Programmed cell death-1 (PD-1) is a potent immune checkpoint receptor on T lymphocytes. Upon engagement by its ligands, PD-L1 or PD-L2, PD-1 inhibits T cell activation and can promote immune tolerance. Antagonism of PD-1 signaling has proven effective in cancer immunotherapy, and conversely, agonists of the receptor may have a role in treating autoimmune disease. Some immune receptors function as dimers
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Recurrent infections drive persistent bladder dysfunction and pain via sensory nerve sprouting and mast cell activity Sci. Immunol (IF 24.8) Pub Date : 2024-03-01 Byron W. Hayes, Hae Woong Choi, Abhay P.S. Rathore, Chunjing Bao, Jianling Shi, Yul Huh, Michael W. Kim, Andrea Mencarelli, Pradeep Bist, Lai Guan Ng, Changming Shi, Joo Hwan Nho, Aram Kim, Hana Yoon, Donghoon Lim, Johanna L. Hannan, J. Todd Purves, Francis M. HughesJr., Ru-Rong Ji, Soman N. Abraham
Urinary tract infections (UTIs) account for almost 25% of infections in women. Many are recurrent (rUTI), with patients frequently experiencing chronic pelvic pain and urinary frequency despite clearance of bacteriuria after antibiotics. To elucidate the basis for these bacteria-independent bladder symptoms, we examined the bladders of patients with rUTI. We noticed a notable increase in neuropeptide
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Recurrent infections drive persistent bladder dysfunction and pain via sensory nerve sprouting and mast cell activity Sci. Immunol (IF 24.8) Pub Date : 2024-03-01 Byron W. Hayes, Hae Woong Choi, Abhay P.S. Rathore, Chunjing Bao, Jianling Shi, Yul Huh, Michael W. Kim, Andrea Mencarelli, Pradeep Bist, Lai Guan Ng, Changming Shi, Joo Hwan Nho, Aram Kim, Hana Yoon, Donghoon Lim, Johanna L. Hannan, J. Todd Purves, Francis M. Hughes, Ru-Rong Ji, Soman N. Abraham
Urinary tract infections (UTIs) account for almost 25% of infections in women. Many are recurrent (rUTI), with patients frequently experiencing chronic pelvic pain and urinary frequency despite clearance of bacteriuria after antibiotics. To elucidate the basis for these bacteria-independent bladder symptoms, we examined the bladders of patients with rUTI. We noticed a notable increase in neuropeptide
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TGF-β specifies T FH versus T H 17 cell fates in murine CD4 + T cells through c-Maf Sci. Immunol (IF 24.8) Pub Date : 2024-03-01 Yinshui Chang, Luisa Bach, Marko Hasiuk, Lifen Wen, Tarek Elmzzahi, Carlson Tsui, Nicolás Gutiérrez-Melo, Teresa Steffen, Daniel T. Utzschneider, Timsse Raj, Paul Jonas Jost, Sylvia Heink, Jingyuan Cheng, Oliver T. Burton, Julia Zeiträg, Dominik Alterauge, Frank Dahlström, Jennifer-Christin Becker, Melanie Kastl, Konstantinos Symeonidis, Martina van Uelft, Matthias Becker, Sarah Reschke, Stefan Krebs
T follicular helper (T FH ) cells are essential for effective antibody responses, but deciphering the intrinsic wiring of mouse T FH cells has long been hampered by the lack of a reliable protocol for their generation in vitro. We report that transforming growth factor–β (TGF-β) induces robust expression of T FH hallmark molecules CXCR5 and Bcl6 in activated mouse CD4 + T cells in vitro. TGF-β–induced
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Mast cells help organize the Peyer’s patch niche for induction of IgA responses Sci. Immunol (IF 24.8) Pub Date : 2024-03-01 Marco De Giovanni, Vivasvan S. Vykunta, Adi Biram, Kevin Y. Chen, Hanna Taglinao, Jinping An, Dean Sheppard, Helena Paidassi, Jason G. Cyster
Peyer’s patches (PPs) are lymphoid structures situated adjacent to the intestinal epithelium that support B cell responses that give rise to many intestinal IgA-secreting cells. Induction of isotype switching to IgA in PPs requires interactions between B cells and TGFβ-activating conventional dendritic cells type 2 (cDC2s) in the subepithelial dome (SED). However, the mechanisms promoting cDC2 positioning
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The gene regulatory basis of bystander activation in CD8 + T cells Sci. Immunol (IF 24.8) Pub Date : 2024-02-23 Neva B. Watson, Ravi K. Patel, Connor Kean, Janelle Veazey, Oyebola O. Oyesola, Nathan Laniewski, Jennifer K. Grenier, Jocelyn Wang, Cybelle Tabilas, Kristel J. Yee Mon, Adrian J. McNairn, Seth A. Peng, Samantha P. Wesnak, Kito Nzingha, Miles P. Davenport, Elia D. Tait Wojno, Kristin M. Scheible, Norah L. Smith, Andrew Grimson, Brian D. Rudd
CD8 + T cells are classically recognized as adaptive lymphocytes based on their ability to recognize specific foreign antigens and mount memory responses. However, recent studies indicate that some antigen-inexperienced CD8 + T cells can respond to innate cytokines alone in the absence of cognate T cell receptor stimulation, a phenomenon referred to as bystander activation. Here, we demonstrate that
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T cell help shapes B cell tolerance Sci. Immunol (IF 24.8) Pub Date : 2024-02-16 Elliot H. Akama-Garren, Xihui Yin, Tyler R. Prestwood, Minghe Ma, Paul J. Utz, Michael C. Carroll
T cell help is a crucial component of the normal humoral immune response, yet whether it promotes or restrains autoreactive B cell responses remains unclear. Here, we observe that autoreactive germinal centers require T cell help for their formation and persistence. Using retrogenic chimeras transduced with candidate TCRs, we demonstrate that a follicular T cell repertoire restricted to a single autoreactive
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STING licensing of type I dendritic cells potentiates antitumor immunity Sci. Immunol (IF 24.8) Pub Date : 2024-02-16 Jian Wang, Suxin Li, Maggie Wang, Xu Wang, Shuqing Chen, Zhichen Sun, Xiubao Ren, Gang Huang, Baran D. Sumer, Nan Yan, Yang-Xin Fu, Jinming Gao
Stimulator of interferon genes (STING) is an immune adaptor protein that senses cyclic GMP-AMP in response to self or microbial cytosolic DNA as a danger signal. STING is ubiquitously expressed in diverse cell populations, including cancer cells, with distinct cellular functions, such as activation of type I interferons, autophagy induction, or triggering apoptosis. It is not well understood whether
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Progressive accumulation of hyperinflammatory NKG2D low NK cells in early childhood severe atopic dermatitis Sci. Immunol (IF 24.8) Pub Date : 2024-02-09 David E. Ochayon, Stanley B. DeVore, Wan-Chi Chang, Durga Krishnamurthy, Harsha Seelamneni, Brittany Grashel, Daniel Spagna, Sandra Andorf, Lisa J. Martin, Jocelyn M. Biagini, Stephen N. Waggoner, Gurjit K. Khurana Hershey
Atopic dermatitis (AD) is a chronic inflammatory skin disease that often precedes the development of food allergy, asthma, and allergic rhinitis. The prevailing paradigm holds that a reduced frequency and function of natural killer (NK) cell contributes to AD pathogenesis, yet the underlying mechanisms and contributions of NK cells to allergic comorbidities remain ill-defined. Here, analysis of circulating
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Mucosal and systemic immune correlates of viral control after SARS-CoV-2 infection challenge in seronegative adults Sci. Immunol (IF 24.8) Pub Date : 2024-02-09 Helen R. Wagstaffe, Ryan S. Thwaites, Arnold Reynaldi, Jasmin K. Sidhu, Richard McKendry, Stephanie Ascough, Loukas Papargyris, Ashley M. Collins, Jiayun Xu, Nana-Marie Lemm, Matthew K. Siggins, Benny M. Chain, Ben Killingley, Mariya Kalinova, Alex Mann, Andrew Catchpole, Miles P. Davenport, Peter J. M. Openshaw, Christopher Chiu
Human infection challenge permits in-depth, early, and pre-symptomatic characterization of the immune response, enabling the identification of factors that are important for viral clearance. Here, we performed intranasal inoculation of 34 young adult, seronegative volunteers with a pre-Alpha severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain. Of these participants, 18 (53%) became
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BCL6 is required for the thymic development of TCRαβ + CD8αα + intraepithelial lymphocyte lineage Sci. Immunol (IF 24.8) Pub Date : 2024-02-09 Qi Xing, Dehui Chang, Shiyuan Xie, Xiaohong Zhao, Hao Zhang, Xiaohu Wang, Xue Bai, Chen Dong
TCRαβ + CD8αα + intraepithelial lymphocytes (CD8αα + αβ IELs) are a specialized subset of T cells in the gut epithelium that develop from thymic agonist selected IEL precursors (IELps). The molecular mechanisms underlying the selection and differentiation of this T cell type in the thymus are largely unknown. Here, we found that Bcl6 deficiency in αβ T cells resulted in the near absence of CD8αα +
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Zeb2 drives the formation of CD11c + atypical B cells to sustain germinal centers that control persistent infection Sci. Immunol (IF 24.8) Pub Date : 2024-02-08 Xin Gao, Qian Shen, Jonathan A. Roco, Becan Dalton, Katie Frith, C. Mee Ling Munier, Fiona D. Ballard, Ke Wang, Hannah G. Kelly, Maxim Nekrasov, Jin-Shu He, Rebecca Jaeger, Patricia Carreira, Julia I. Ellyard, Lynette Beattie, Anselm Enders, Matthew C. Cook, John J. Zaunders, Ian A. Cockburn
CD11c + atypical B cells (ABCs) are an alternative memory B cell lineage associated with immunization, infection, and autoimmunity. However, the factors that drive the transcriptional program of ABCs have not been identified, and the function of this population remains incompletely understood. Here we identified candidate transcription factors associated with the ABC population based on a human tonsillar
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Age-associated CD4 + T cells with B cell-promoting functions are regulated by ZEB2 in autoimmunity Sci. Immunol (IF 24.8) Pub Date : 2024-02-08 Manaka Goto, Hideyuki Takahashi, Ryochi Yoshida, Takahiro Itamiya, Masahiro Nakano, Yasuo Nagafuchi, Hiroaki Harada, Toshiaki Shimizu, Meiko Maeda, Akatsuki Kubota, Tatsushi Toda, Hiroaki Hatano, Yusuke Sugimori, Kimito Kawahata, Kazuhiko Yamamoto, Hirofumi Shoda, Kazuyoshi Ishigaki, Mineto Ota, Tomohisa Okamura, Keishi Fujio
Aging is a significant risk factor for autoimmunity, and many autoimmune diseases tend to onset during adulthood. We conducted an extensive analysis of CD4 + T cell subsets from 354 autoimmune disease patients and healthy controls via flow cytometry and bulk RNA sequencing. As a result, we identified a distinct CXCR3 mid CD4 + effector memory T cell subset that expands with age, which we designated
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A nasal cell atlas reveals heterogeneity of tuft cells and their role in directing olfactory stem cell proliferation Sci. Immunol (IF 24.8) Pub Date : 2024-02-02 Saltanat Ualiyeva, Evan Lemire, Caitlin Wong, Alexander Perniss, Amelia A. Boyd, Evelyn C. Avilés, Dante G. Minichetti, Alice Maxfield, Rachel Roditi, Ichiro Matsumoto, Xin Wang, Wenjiang Deng, Nora A. Barrett, Kathleen M. Buchheit, Tanya M. Laidlaw, Joshua A. Boyce, Lora G. Bankova, Adam L. Haber
The olfactory neuroepithelium serves as a sensory organ for odors and forms part of the nasal mucosal barrier. Olfactory sensory neurons are surrounded and supported by epithelial cells. Among them, microvillous cells (MVCs) are strategically positioned at the apical surface, but their specific functions are enigmatic, and their relationship to the other specialized epithelial cells is unclear. Here
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Precise CRISPR-Cas9 gene repair in autologous memory T cells to treat familial hemophagocytic lymphohistiocytosis Sci. Immunol (IF 24.8) Pub Date : 2024-02-02 Xun Li, Tristan Wirtz, Timm Weber, Mikhail Lebedin, Elijah D. Lowenstein, Thomas Sommermann, Andreas Zach, Tomoharu Yasuda, Kathrin de la Rosa, Van Trung Chu, Johannes H. Schulte, Ingo Müller, Christine Kocks, Klaus Rajewsky
Familial hemophagocytic lymphohistiocytosis (FHL) is an inherited, often fatal immune deficiency characterized by severe systemic hyperinflammation. Although allogeneic bone marrow transplantation can be curative, more effective therapies are urgently needed. FHL is caused by inactivating mutations in proteins that regulate cellular immunity. Here, we used an adeno-associated virus–based CRISPR-Cas9
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Response to tumor-infiltrating lymphocyte adoptive therapy is associated with preexisting CD8 + T-myeloid cell networks in melanoma Sci. Immunol (IF 24.8) Pub Date : 2024-02-02 David Barras, Eleonora Ghisoni, Johanna Chiffelle, Angela Orcurto, Julien Dagher, Noémie Fahr, Fabrizio Benedetti, Isaac Crespo, Alizée J. Grimm, Matteo Morotti, Stefan Zimmermann, Rafael Duran, Martina Imbimbo, Maria Ochoa de Olza, Blanca Navarro, Krisztian Homicsko, Sara Bobisse, Danny Labes, Zoe Tsourti, Charitini Andriakopoulou, Fernanda Herrera, Rémy Pétremand, Reinhard Dummer, Gregoire Berthod
Adoptive cell therapy (ACT) using ex vivo–expanded tumor-infiltrating lymphocytes (TILs) can eliminate or shrink metastatic melanoma, but its long-term efficacy remains limited to a fraction of patients. Using longitudinal samples from 13 patients with metastatic melanoma treated with TIL-ACT in a phase 1 clinical study, we interrogated cellular states within the tumor microenvironment (TME) and their
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A single-cell atlas of IL-23 inhibition in cutaneous psoriasis distinguishes clinical response Sci. Immunol (IF 24.8) Pub Date : 2024-01-26 David Wu, Ashley A. Hailer, Sijia Wang, Michelle Yuan, Jamie Chan, Abdullah El Kurdi, David Han, Hira Ali, Blaize D’Angio, Aaron Mayer, Maha Rahim, Ayano Kondo, Daniel Klufas, Esther Kim, A. Hunter Shain, Jaehyuk Choi, Tina Bhutani, Gregory Simpson, Roy C. Grekin, Roberto Ricardo-Gonzalez, Elizabeth Purdom, Jeffrey P. North, Jeffrey B. Cheng, Raymond J. Cho
Psoriasis vulgaris and other chronic inflammatory diseases improve markedly with therapeutic blockade of interleukin-23 (IL-23) signaling, but the genetic mechanisms underlying clinical responses remain poorly understood. Using single-cell transcriptomics, we profiled immune cells isolated from lesional psoriatic skin before and during IL-23 blockade. In clinically responsive patients, a psoriatic
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Sulfated bile acid is a host-derived ligand for MAIT cells Sci. Immunol (IF 24.8) Pub Date : 2024-01-26 Emi Ito, Shinsuke Inuki, Yoshihiro Izumi, Masatomo Takahashi, Yuki Dambayashi, Lisa Ciacchi, Wael Awad, Ami Takeyama, Kensuke Shibata, Shotaro Mori, Jeffrey Y. W. Mak, David P. Fairlie, Takeshi Bamba, Eri Ishikawa, Masamichi Nagae, Jamie Rossjohn, Sho Yamasaki
Mucosal-associated invariant T (MAIT) cells are innate-like T cells that recognize bacterial riboflavin–based metabolites as activating antigens. Although MAIT cells are found in tissues, it is unknown whether any host tissue–derived antigens exist. Here, we report that a sulfated bile acid, cholic acid 7-sulfate (CA7S), binds the nonclassical MHC class I protein MR1 and is recognized by MAIT cells
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Omicron BA.2 breakthrough infection elicits CD8 + T cell responses recognizing the spike of later Omicron subvariants Sci. Immunol (IF 24.8) Pub Date : 2024-01-19 Sang-Hoon Kim, Jihye Kim, Sungmin Jung, Ji Yun Noh, Jinnam Kim, Heedo Park, Young Goo Song, Kyong Ran Peck, Su-Hyung Park, Man-Seong Park, Jae-Hoon Ko, Joon Young Song, Jun Yong Choi, Min Kyung Jung, Eui-Cheol Shin
Here, we examine peripheral blood memory T cell responses against the SARS-CoV-2 BA.4/BA.5 variant spike among vaccinated individuals with or without Omicron breakthrough infections. We provide evidence supporting a lack of original antigenic sin in CD8 + T cell responses targeting the spike. We show that BNT162b2-induced memory T cells respond to the BA.4/BA.5 spike. Among individuals with BA.1/BA
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TGFβ prevents IgE-mediated allergic disease by restraining T follicular helper 2 differentiation Sci. Immunol (IF 24.8) Pub Date : 2024-01-19 Tamara T. Haque, Katherine A. Weissler, Zoe Schmiechen, Karen Laky, Daniella M. Schwartz, Jenny Li, Michela Locci, Mathilde Turfkruyer, Chen Yao, Paul Schaughency, Lashawna Leak, Justin Lack, Yuka Kanno, John O’Shea, Pamela A. Frischmeyer-Guerrerio
Allergic diseases are common, affecting more than 20% of the population. Genetic variants in the TGFβ pathway are strongly associated with atopy. To interrogate the mechanisms underlying this association, we examined patients and mice with Loeys-Dietz syndrome (LDS) who harbor missense mutations in the kinase domain of TGFΒR1/2 . We demonstrate that LDS mutations lead to reduced TGFβ signaling and
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CD4 + T cell immunity against cutaneous melanoma encompasses multifaceted MHC II–dependent responses Sci. Immunol (IF 24.8) Pub Date : 2024-01-19 Emma G. Bawden, Teagan Wagner, Jan Schröder, Maike Effern, Daniel Hinze, Lewis Newland, Grace H. Attrill, Ariane R. Lee, Sven Engel, David Freestone, Marcela de Lima Moreira, Elise Gressier, Nathan McBain, Annabell Bachem, Ashraful Haque, Ruining Dong, Angela L. Ferguson, Jarem J. Edwards, Peter M. Ferguson, Richard A. Scolyer, James S. Wilmott, Christopher M. Jewell, Andrew G. Brooks, David E. Gyorki
Whereas CD4 + T cells conventionally mediate antitumor immunity by providing help to CD8 + T cells, recent clinical studies have implied an important role for cytotoxic CD4 + T cells in cancer immunity. Using an orthotopic melanoma model, we provide a detailed account of antitumoral CD4 + T cell responses and their regulation by major histocompatibility complex class II (MHC II) in the skin. Intravital
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Tuft cells and fibroblasts promote thymus regeneration through ILC2-mediated type 2 immune response Sci. Immunol (IF 24.8) Pub Date : 2024-01-12 Shir Nevo, Noga Frenkel, Noam Kadouri, Tom Gome, Noa Rosenthal, Tal Givony, Ayelet Avin, Cristina Peligero Cruz, Merav Kedmi, Moshit Lindzen, Shifra Ben Dor, Golda Damari, Ziv Porat, Rebecca Haffner-Krausz, Hadas Keren-Shaul, Yosef Yarden, Ariel Munitz, Dena Leshkowitz, Yael Goldfarb, Jakub Abramson
The thymus is a primary lymphoid organ that is essential for the establishment of adaptive immunity through generation of immunocompetent T cells. In response to various stress signals, the thymus undergoes acute but reversible involution. However, the mechanisms governing its recovery are incompletely understood. Here, we used a dexamethasone-induced acute thymic involution mouse model to investigate
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Non-apoptotic FAS signaling controls mTOR activation and extrafollicular maturation in human B cells Sci. Immunol (IF 24.8) Pub Date : 2024-01-12 Julian Staniek, Tomas Kalina, Geoffroy Andrieux, Melanie Boerries, Iga Janowska, Manuel Fuentes, Paula Díez, Marina Bakardjieva, Jitka Stancikova, Jan Raabe, Julika Neumann, Sabine Schwenk, Leonardo Arpesella, Jan Stuchly, Vladimir Benes, Rodrigo García Valiente, Jonatan Fernández García, Rita Carsetti, Eva Piano Mortari, Albert Catala, Oscar de la Calle, Georgios Sogkas, Bénédicte Neven, Frédéric
Defective FAS (CD95/Apo-1/TNFRSF6) signaling causes autoimmune lymphoproliferative syndrome (ALPS). Hypergammaglobulinemia is a common feature in ALPS with FAS mutations (ALPS-FAS), but paradoxically, fewer conventional memory cells differentiate from FAS-expressing germinal center (GC) B cells. Resistance to FAS-induced apoptosis does not explain this phenotype. We tested the hypothesis that defective
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Disrupted degradative sorting of TLR7 is associated with human lupus Sci. Immunol (IF 24.8) Pub Date : 2024-01-11 Harshita Mishra, Claire Schlack-Leigers, Ee Lyn Lim, Oliver Thieck, Thomas Magg, Johannes Raedler, Christine Wolf, Christoph Klein, Helge Ewers, Min Ae Lee-Kirsch, David Meierhofer, Fabian Hauck, Olivia Majer
Hyperactive TLR7 signaling has long been appreciated as driver of autoimmune disease in mouse models. Recently, gain-of-function mutations in TLR7 were identified as a monogenic cause of human lupus. TLR7 is an intracellular transmembrane receptor, sensing RNA breakdown products within late endosomes. Here, we show that endosome dysfunction leads to unrestricted TLR7 signaling and is associated with
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UNC93B1 variants underlie TLR7-dependent autoimmunity Sci. Immunol (IF 24.8) Pub Date : 2024-01-11 Christine Wolf, Ee Lyn Lim, Mohammad Mokhtari, Barbara Kind, Alexandru Odainic, Eusebia Lara-Villacanas, Sarah Koss, Simon Mages, Katharina Menzel, Kerstin Engel, Gregor Dückers, Benedikt Bernbeck, Dominik T. Schneider, Kathrin Siepermann, Tim Niehues, Carl Christoph Goetzke, Pawel Durek, Kirsten Minden, Thomas Dörner, Anna Stittrich, Franziska Szelinski, Gabriela Maria Guerra, Mona Massoud, Markus
UNC93B1 is critical for trafficking and function of nucleic acid-sensing Toll-like receptors (TLR) TLR3, TLR7, TLR8, and TLR9, which are essential for antiviral immunity. Overactive TLR7 signaling induced by recognition of self-nucleic acids has been implicated in systemic lupus erythematosus (SLE). Here, we report UNC93B1 variants (E92G, R336L) in four patients with early-onset SLE. Patient cells
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A dynamic atlas of immunocyte migration from the gut Sci. Immunol (IF 24.8) Pub Date : 2024-01-05 Silvia Galván-Peña, Yangyang Zhu, Bola S. Hanna, Diane Mathis, Christophe Benoist
Dysbiosis in the gut microbiota affects several systemic diseases, possibly by driving the migration of perturbed intestinal immunocytes to extraintestinal tissues. Combining Kaede photoconvertible mice and single-cell genomics, we generated a detailed map of migratory trajectories from the colon, at baseline, and in several models of intestinal and extraintestinal inflammation. All lineages emigrated
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In a wild germinal center, what determines survival of the fittest? Sci. Immunol (IF 24.8) Pub Date : 2024-01-05 Emily M. Flowers, Stephanie C. Eisenbarth
Mice with natural BCR frequencies have plasma cells enriched for high-affinity clones, but high-affinity clones persist in the germinal center, leaving the rules for plasma cell selection still murky.
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Regulatory T cells in skin mediate immune privilege of the hair follicle stem cell niche Sci. Immunol (IF 24.8) Pub Date : 2024-01-05 Jarish N. Cohen, Victoire Gouirand, Courtney E. Macon, Margaret M. Lowe, Ian C. Boothby, Joshua M. Moreau, Iris K. Gratz, Angelika Stoecklinger, Casey T. Weaver, Arlene H. Sharpe, Roberto R. Ricardo-Gonzalez, Michael D. Rosenblum
Immune tolerance is maintained in lymphoid organs (LOs). Despite the presence of complex immune cell networks in non-LOs, it is unknown whether self-tolerance is maintained in these tissues. We developed a technique to restrict genetic recombination to regulatory T cells (T regs ) only in skin. Selective depletion of skin T regs resulted in T cell–mediated inflammation of hair follicles (HFs). Suppression
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LITAF protects against pore-forming protein–induced cell death by promoting membrane repair Sci. Immunol (IF 24.8) Pub Date : 2024-01-05 Caroline Stefani, Anna M. Bruchez, Mario G. Rosasco, Anna E. Yoshida, Kayla J. Fasano, Paula F. Levan, Alina Lorant, Nicholas W. Hubbard, Andrew Oberst, Lynda M. Stuart, Adam Lacy-Hulbert
Pore-forming toxins (PFTs) are the largest class of bacterial toxins and contribute to virulence by triggering host cell death. Vertebrates also express endogenous pore-forming proteins that induce cell death as part of host defense. To mitigate damage and promote survival, cells mobilize membrane repair mechanisms to neutralize and counteract pores, but how these pathways are activated is poorly understood
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KCNN4 links PIEZO-dependent mechanotransduction to NLRP3 inflammasome activation Sci. Immunol (IF 24.8) Pub Date : 2023-12-22 Li Ran, Tao Ye, Eric Erbs, Stephan Ehl, Nathalie Spassky, Izabela Sumara, Zhirong Zhang, Romeo Ricci
Immune cells sense the microenvironment to fine-tune their inflammatory responses. Patients with cryopyrin-associated periodic syndrome (CAPS), caused by mutations in the NLRP3 gene, develop autoinflammation triggered by nonantigenic cues such as from the environment. However, the underlying mechanisms are poorly understood. Here, we uncover that KCNN4, a calcium-activated potassium channel, links
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Exocrine gland–resident memory CD8 + T cells use mechanosensing for tissue surveillance Sci. Immunol (IF 24.8) Pub Date : 2023-12-22 Nora Ruef, Jose Martínez Magdaleno, Xenia Ficht, Vladimir Purvanov, Matthieu Palayret, Stefanie Wissmann, Petra Pfenninger, Bettina Stolp, Flavian Thelen, Juliana Barreto de Albuquerque, Philipp Germann, James Sharpe, Jun Abe, Daniel F. Legler, Jens V. Stein
Tissue-resident CD8 + T cells (T RM ) continuously scan peptide-MHC (pMHC) complexes in their organ of residence to intercept microbial invaders. Recent data showed that T RM lodged in exocrine glands scan tissue in the absence of any chemoattractant or adhesion receptor signaling, thus bypassing the requirement for canonical migration-promoting factors. The signals eliciting this noncanonical motility
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Acquisition of suppressive function by conventional T cells limits antitumor immunity upon T reg depletion Sci. Immunol (IF 24.8) Pub Date : 2023-12-15 Sarah K. Whiteside, Francis M. Grant, Giorgia Alvisi, James Clarke, Leqi Tang, Charlotte J. Imianowski, Baojie Zhang, Alexander C. Evans, Alexander J. Wesolowski, Alberto G. Conti, Jie Yang, Sarah N. Lauder, Mathew Clement, Ian R. Humphreys, James Dooley, Oliver Burton, Adrian Liston, Marco Alloisio, Emanuele Voulaz, Jean Langhorne, Klaus Okkenhaug, Enrico Lugli, Rahul Roychoudhuri
Regulatory T (T reg ) cells contribute to immune homeostasis but suppress immune responses to cancer. Strategies to disrupt T reg cell–mediated cancer immunosuppression have been met with limited clinical success, but the underlying mechanisms for treatment failure are poorly understood. By modeling T reg cell–targeted immunotherapy in mice, we find that CD4 + Foxp3 − conventional T (T conv ) cells
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Early human lung immune cell development and its role in epithelial cell fate Sci. Immunol (IF 24.8) Pub Date : 2023-12-15 Josephine L. Barnes, Masahiro Yoshida, Peng He, Kaylee B. Worlock, Rik G.H. Lindeboom, Chenqu Suo, J. Patrick Pett, Anna Wilbrey-Clark, Emma Dann, Lira Mamanova, Laura Richardson, Krzysztof Polanski, Adam Pennycuick, Jessica Allen-Hyttinen, Iván T. Herczeg, Romina Arzili, Robert E. Hynds, Vitor H. Teixeira, Muzlifah Haniffa, Kyungtae Lim, Dawei Sun, Emma L. Rawlins, Amanda J. Oliver, Paul A. Lyons
Studies of human lung development have focused on epithelial and mesenchymal cell types and function, but much less is known about the developing lung immune cells, even though the airways are a major site of mucosal immunity after birth. An unanswered question is whether tissue-resident immune cells play a role in shaping the tissue as it develops in utero. Here, we profiled human embryonic and fetal
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Antigen-specific memory NK cell responses against HIV and influenza use the NKG2/HLA-E axis Sci. Immunol (IF 24.8) Pub Date : 2023-12-08 Stephanie Jost, Olivier Lucar, Esther Lee, Taylor Yoder, Kyle Kroll, Sho Sugawara, Scott Smith, Rhianna Jones, George Tweet, Alexandra Werner, Phillip J. Tomezsko, Haley L. Dugan, Joshua Ghofrani, Philippe Rascle, Marcus Altfeld, Michaela Müller-Trutwin, Paul Goepfert, R. Keith Reeves
Multiple studies have broadened the roles of natural killer (NK) cells functioning as purely innate lymphocytes by demonstrating that they are capable of putative antigen-specific immunological memory against multiple infectious agents including HIV-1 and influenza. However, the mechanisms underlying antigen specificity remain unknown. Here, we demonstrate that antigen-specific human NK cell memory
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SARS-CoV-2 vaccination enhances the effector qualities of spike-specific T cells induced by COVID-19 Sci. Immunol (IF 24.8) Pub Date : 2023-12-08 Curtis Cai, Yu Gao, Sarah Adamo, Olga Rivera-Ballesteros, Lotta Hansson, Anders Österborg, Peter Bergman, Johan K. Sandberg, Hans-Gustaf Ljunggren, Niklas K. Björkström, Kristoffer Strålin, Sian Llewellyn-Lacey, David A. Price, Chuan Qin, Alba Grifoni, Daniela Weiskopf, E. John Wherry, Alessandro Sette, Soo Aleman, Marcus Buggert
T cells are critical for immune protection against severe COVID-19, but it has remained unclear whether repeated exposure to SARS-CoV-2 antigens delivered in the context of vaccination fuels T cell exhaustion or reshapes T cell functionality. Here, we sampled convalescent donors with a history of mild or severe COVID-19 before and after SARS-CoV-2 vaccination to profile the functional spectrum of hybrid
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CD8 T regs SQa-1shing transplant rejection Sci. Immunol (IF 24.8) Pub Date : 2023-12-01 Nathan A. Bracey, Jonathan S. Maltzman
MHC-E restricted CD8 + regulatory T cells have a restricted TCR repertoire and eliminate pathogenic CD4 T cells to mediate immune responses.
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Structural principles of peptide-centric chimeric antigen receptor recognition guide therapeutic expansion Sci. Immunol (IF 24.8) Pub Date : 2023-12-01 Yi Sun, Tyler J. Florio, Sagar Gupta, Michael C. Young, Quinlen F. Marshall, Samuel E. Garfinkle, Georgia F. Papadaki, Hau V. Truong, Emily Mycek, Peiyao Li, Alvin Farrel, Nicole L. Church, Shereen Jabar, Matthew D. Beasley, Ben R. Kiefel, Mark Yarmarkovich, Leena Mallik, John M. Maris, Nikolaos G. Sgourakis
Peptide-centric chimeric antigen receptors (PC-CARs) recognize oncoprotein epitopes displayed by cell-surface human leukocyte antigens (HLAs) and offer a promising strategy for targeted cancer therapy. We have previously developed a PC-CAR targeting a neuroblastoma-associated PHOX2B peptide, leading to robust tumor cell lysis restricted by two common HLA allotypes. Here, we determine the 2.1-angstrom
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Listen to your gut: Antibodies against gut commensals predict type 1 diabetes onset and therapeutic responses to T cell modulation Sci. Immunol (IF 24.8) Pub Date : 2023-12-01 Rachael A. Clark
Immune responses to gut bacteria are associated with development of type 1 diabetes and predict the effectiveness of teplizumab, an anti-CD3 antibody, in delaying diabetes onset.
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The chilling origin of germinal centers Sci. Immunol (IF 24.8) Pub Date : 2023-12-01 Thomas Boehm
Germinal center–like structures have been identified in ectothermic vertebrates, establishing germinal centers as a universal component of humoral immunity (see related Research Article by Shibasaki et al. )
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Noncanonical MAVS signaling restrains dendritic cell–driven antitumor immunity by inhibiting IL-12 Sci. Immunol (IF 24.8) Pub Date : 2023-12-01 Lingling Wu, Xiaochuan Hong, Chao Yang, Yuanqin Yang, Wenwen Li, Lu Lu, Meichun Cai, Dongqing Cao, Guanglei Zhuang, Liufu Deng
Mitochondrial antiviral signaling protein (MAVS)–mediated cytosolic RNA sensing plays a central role in tumor immunogenicity. However, the effects of host MAVS signaling on antitumor immunity remain unclear. Here, we demonstrate that the host MAVS pathway supports tumor growth and impairs antitumor immunity, whereas MAVS deficiency in dendritic cells (DCs) promotes tumor-reactive CD8 + T cell responses
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Myeloid OTULIN deficiency couples RIPK3-dependent cell death to Nlrp3 inflammasome activation and IL-1β secretion Sci. Immunol (IF 24.8) Pub Date : 2023-11-24 M. Giulia Doglio, Lien Verboom, Emily Ruilova Sosoranga, Ulrika C. Frising, Tomoko Asaoka, Yannick Gansemans, Filip Van Nieuwerburgh, Geert van Loo, Andy Wullaert
Loss-of-function mutations in the deubiquitinase OTULIN result in an inflammatory pathology termed “OTULIN-related autoinflammatory syndrome” (ORAS). Genetic mouse models revealed essential roles for OTULIN in inflammatory and cell death signaling, but the mechanisms by which OTULIN deficiency connects cell death to inflammation remain unclear. Here, we identify OTULIN deficiency as a cellular condition
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Emergence and fate of stem cell–like Tcf7 + CD8 + T cells during a primary immune response to viral infection Sci. Immunol (IF 24.8) Pub Date : 2023-11-17 Joana Gomes Silva, Daniela Pais Ferreira, Alexandre Dumez, Tania Wyss, Romain Veber, Maxime Danilo, Daniel D. Pinschewer, Mélanie Charmoy, Werner Held
In response to infection, naïve CD8 + T (T N ) cells yield a large pool of short-lived terminal effector (T TE ) cells that eliminate infected host cells. In parallel, a minor population of stem cell–like central memory (T CM ) cells forms, which has the capacity to maintain immunity after pathogen clearance. It has remained uncertain whether stem-like T CM cells arise by dedifferentiation from a subset
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Cancer immunotherapy via synergistic coactivation of myeloid receptors CD40 and Dectin-1 Sci. Immunol (IF 24.8) Pub Date : 2023-11-17 Max M. Wattenberg, Heather Coho, Veronica M. Herrera, Kathleen Graham, Meredith L. Stone, Yuqing Xue, Renee B. Chang, Christopher Cassella, Mingen Liu, Shaanti Choi-Bose, Stacy K. Thomas, Hana Choi, Yan Li, Kelly Markowitz, Lauren Melendez, Michael Gianonne, Nandita Bose, Gregory L. Beatty
Myeloid cells facilitate T cell immune evasion in cancer yet are pliable and have antitumor potential. Here, by cotargeting myeloid activation molecules, we leveraged the myeloid compartment as a therapeutic vulnerability in mouse models of pancreatic cancer. Myeloid cells in solid tumors expressed activation receptors including the pattern recognition receptor Dectin-1 and the TNF receptor superfamily
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Enhanced SARS-CoV-2 humoral immunity following breakthrough infection builds upon the preexisting memory B cell pool Sci. Immunol (IF 24.8) Pub Date : 2023-11-17 Timm Weber, Sabrina Dähling, Svea Rose, Patrick Affeldt, Kanika Vanshylla, Leon Ullrich, Lutz Gieselmann, Finn Teipel, Henning Gruell, Veronica Di Cristanziano, Dae Sung Kim, George Georgiou, Manuel Koch, Christoph Kreer, Florian Klein
The human immune response must continuously adapt to newly emerging SARS-CoV-2 variants. To investigate how B cells respond to repeated SARS-CoV-2 antigen exposure by Wu01 booster vaccination and Omicron breakthrough infection, we performed a molecular longitudinal analysis of the memory B cell pool. We demonstrate that a subsequent breakthrough infection substantially increases the frequency of B
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Transcriptomes and metabolism define mouse and human MAIT cell populations Sci. Immunol (IF 24.8) Pub Date : 2023-11-10 Shilpi Chandra, Gabriel Ascui, Thomas Riffelmacher, Ashu Chawla, Ciro Ramírez-Suástegui, Viankail C. Castelan, Gregory Seumois, Hayley Simon, Mallory P. Murray, Goo-Young Seo, Ashmitaa L. R. Premlal, Benjamin Schmiedel, Greet Verstichel, Yingcong Li, Chia-Hao Lin, Jason Greenbaum, John Lamberti, Raghav Murthy, John Nigro, Hilde Cheroutre, Christian H. Ottensmeier, Stephen M. Hedrick, Li-Fan Lu, Pandurangan
Mucosal-associated invariant T (MAIT) cells are a subset of T lymphocytes that respond to microbial metabolites. We defined MAIT cell populations in different organs and characterized the developmental pathway of mouse and human MAIT cells in the thymus using single-cell RNA sequencing and phenotypic and metabolic analyses. We showed that the predominant mouse subset, which produced IL-17 (MAIT17)
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Zfp281 and Zfp148 control CD4 + T cell thymic development and T H 2 functions Sci. Immunol (IF 24.8) Pub Date : 2023-11-10 Laura B. Chopp, Xiaoliang Zhu, Yayi Gao, Jia Nie, Jatinder Singh, Parimal Kumar, Kelly Z. Young, Shil Patel, Caiyi Li, Mariah Balmaceno-Criss, Melanie S. Vacchio, Michael M. Wang, Ferenc Livak, Juanita L. Merchant, Lie Wang, Michael C. Kelly, Jinfang Zhu, Rémy Bosselut
How CD4 + lineage gene expression is initiated in differentiating thymocytes remains poorly understood. Here, we show that the paralog transcription factors Zfp281 and Zfp148 control both this process and cytokine expression by T helper cell type 2 (T H 2) effector cells. Genetic, single-cell, and spatial transcriptomic analyses showed that these factors promote the intrathymic CD4 + T cell differentiation
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Distinct use of super-enhancer elements controls cell type–specific CD25 transcription and function Sci. Immunol (IF 24.8) Pub Date : 2023-11-03 Rosanne Spolski, Peng Li, Vivek Chandra, Boyoung Shin, Shubham Goel, Keiko Sakamoto, Chengyu Liu, Jangsuk Oh, Min Ren, Yutaka Enomoto, Erin E. West, Stephen M. Christensen, Edwin C. K. Wan, Meili Ge, Jian-Xin Lin, Bingyu Yan, Majid Kazemian, Zu-Xi Yu, Keisuke Nagao, Pandurangan Vijayanand, Ellen V. Rothenberg, Warren J. Leonard
The IL-2 receptor α chain (IL-2Rα/CD25) is constitutively expressed on double-negative (DN2/DN3 thymocytes and regulatory T cells (T regs ) but induced by IL-2 on T and natural killer (NK) cells, with Il2ra expression regulated by a STAT5-dependent super-enhancer. We investigated CD25 regulation and function using a series of mice with deletions spanning STAT5-binding elements. Deleting the upstream
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CSF1R-dependent macrophages in the salivary gland are essential for epithelial regeneration after radiation-induced injury Sci. Immunol (IF 24.8) Pub Date : 2023-11-03 John G. McKendrick, Gareth-Rhys Jones, Sonia S. Elder, Erin Watson, Wouter T’Jonck, Ella Mercer, Marlene S. Magalhaes, Cecilia Rocchi, Lizi M. Hegarty, Amanda L. Johnson, Christoph Schneider, Burkhard Becher, Clare Pridans, Neil Mabbott, Zhaoyuan Liu, Florent Ginhoux, Marc Bajenoff, Rebecca Gentek, Calum C. Bain, Elaine Emmerson
The salivary glands often become damaged in individuals receiving radiotherapy for head and neck cancer, resulting in chronic dry mouth. This leads to detrimental effects on their health and quality of life, for which there is no regenerative therapy. Macrophages are the predominant immune cell in the salivary glands and are attractive therapeutic targets due to their unrivaled capacity to drive tissue
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Regulatory T cells shield muscle mitochondria from interferon-γ–mediated damage to promote the beneficial effects of exercise Sci. Immunol (IF 24.8) Pub Date : 2023-11-03 P. Kent Langston, Yizhi Sun, Birgitta A. Ryback, Amber L. Mueller, Bruce M. Spiegelman, Christophe Benoist, Diane Mathis
Exercise enhances physical performance and reduces the risk of many disorders such as cardiovascular disease, type 2 diabetes, dementia, and cancer. Exercise characteristically incites an inflammatory response, notably in skeletal muscles. Although some effector mechanisms have been identified, regulatory elements activated in response to exercise remain obscure. Here, we have addressed the roles of
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Cold-blooded vertebrates evolved organized germinal center like structures Sci. Immunol (IF 24.8) Pub Date : 2023-11-01 Yasuhiro Shibasaki, Sergei Afanasyev, Alvaro Fernández-Montero, Yang Ding, Shota Watanabe, Fumio Takizawa, Jesús Lamas, Francisco Fontenla, José Manuel Leiro, Aleksei Krasnov, Pierre Boudinot, J. Oriol Sunyer
Germinal centers (GCs) or analogous secondary lymphoid microstructures (SLMs) are thought to have evolved in endothermic species. However, living representatives of their ectothermic ancestors can mount potent secondary antibody (Ab) responses upon infection or immunization, despite the apparent lack of SLMs in these cold-blooded vertebrates. How and where adaptive immune responses are induced in ectothermic