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IgA deficiency destabilizes homeostasis toward intestinal microbes and increases systemic immune dysregulation Sci. Immunol (IF 30.63) Pub Date : 2023-05-26 Peyton E. Conrey, Lidiya Denu, Kaitlin C. O’Boyle, Isaiah Rozich, Jamal Green, Jeffrey Maslanka, Jean-Bernard Lubin, Tereza Duranova, Brittany L. Haltzman, Lauren Gianchetti, Derek A. Oldridge, Nina De Luna, Laura A. Vella, David Allman, Jonathan M. Spergel, Ceylan Tanes, Kyle Bittinger, Sarah E. Henrickson, Michael A. Silverman
The ability of most patients with selective immunoglobulin A (IgA) deficiency (SIgAD) to remain apparently healthy has been a persistent clinical conundrum. Compensatory mechanisms, including IgM, have been proposed, yet it remains unclear how secretory IgA and IgM work together in the mucosal system and, on a larger scale, whether the systemic and mucosal anti-commensal responses are redundant or
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Tissue-resident memory T cells mediate mucosal immunity to recurrent urinary tract infection Sci. Immunol (IF 30.63) Pub Date : 2023-05-26 Matthieu Rousseau, Livia Lacerda Mariano, Tracy Canton, Molly A. Ingersoll
Urinary tract infection (UTI) is one of the most prevalent human bacterial infections. New therapeutic approaches, including vaccination and immunotherapy, are urgently needed to combat the rapid global dissemination of multidrug-resistant uropathogens. Development of therapies is impeded by an incomplete understanding of memory development during UTI. Here, we found that reducing bacterial load early
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PD-L1 checkpoint blockade promotes regulatory T cell activity that underlies therapy resistance Sci. Immunol (IF 30.63) Pub Date : 2023-05-19 Mandy van Gulijk, Anneloes van Krimpen, Sjoerd Schetters, Mike Eterman, Marit van Elsas, Joanne Mankor, Larissa Klaase, Marjolein de Bruijn, Menno van Nimwegen, Tim van Tienhoven, Wilfred van Ijcken, Louis Boon, Johan van der Schoot, Martijn Verdoes, Ferenc Scheeren, Sjoerd H. van der Burg, Bart N. Lambrecht, Ralph Stadhouders, Floris Dammeijer, Joachim Aerts, Thorbald van Hall
Despite the clinical success of immune checkpoint blockade (ICB), in certain cancer types, most patients with cancer do not respond well. Furthermore, in patients for whom ICB is initially successful, this is often short-lived because of the development of resistance to ICB. The mechanisms underlying primary or secondary ICB resistance are incompletely understood. Here, we identified preferential activation
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Cytolytic CD8 + T cells infiltrate germinal centers to limit ongoing HIV replication in spontaneous controller lymph nodes Sci. Immunol (IF 30.63) Pub Date : 2023-05-19 David R. Collins, Julia Hitschfel, Jonathan M. Urbach, Geetha H. Mylvaganam, Ngoc L. Ly, Umar Arshad, Zachary J. Racenet, Adrienne G. Yanez, Thomas J. Diefenbach, Bruce D. Walker
Follicular CD8 + T cells (fCD8) mediate surveillance in lymph node (LN) germinal centers against lymphotropic infections and cancers, but the precise mechanisms by which these cells mediate immune control remain incompletely resolved. To address this, we investigated functionality, clonotypic compartmentalization, spatial localization, phenotypic characteristics, and transcriptional profiles of LN-resident
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Efficacy of mRNA-1273 and Novavax ancestral or BA.1 spike booster vaccines against SARS-CoV-2 BA.5 infection in non-human primates Sci. Immunol (IF 30.63) Pub Date : 2023-05-16 Nanda Kishore Routhu, Samuel David Stampfer, Lilin Lai, Akil Akhtar, Xin Tong, Dansu Yuan, Taras M. Chicz, Ryan P. McNamara, Kishor Jakkala, Meredith E. Davis-Gardner, E. Lovisa St Pierre, Brandon Smith, Kristyn Moore Green, Nadia Golden, Breanna Picou, Sherrie M. Jean, Jennifer Wood, Joyce Cohen, Ian N. Moore, Nita Patel, Mimi Guebre-Xabier, Gale Smith, Greg Glenn, Pamela A. Kozlowski, Galit Alter
Omicron SARS-CoV-2 variants escape vaccine-induced neutralizing antibodies and cause nearly all current COVID-19 cases. Here, we compared the efficacy of three booster vaccines against Omicron BA.5 challenge in rhesus macaques: mRNA-1273, the Novavax ancestral spike protein vaccine (NVX-CoV2373), or Omicron BA.1 spike protein version (NVX-CoV2515). All three booster vaccines induced a strong BA.1 cross-reactive
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Genetic mapping reveals Pou2af2/ OCA-T1–dependent tuning of tuft cell differentiation and intestinal type 2 immunity Sci. Immunol (IF 30.63) Pub Date : 2023-05-12 Marija S. Nadjsombati, Natalie Niepoth, Lily M. Webeck, Elizabeth A. Kennedy, Danielle L. Jones, Tyler E. Billipp, Megan T. Baldridge, Andres Bendesky, Jakob von Moltke
Chemosensory epithelial tuft cells contribute to innate immunity at barrier surfaces, but their differentiation from epithelial progenitors is not well understood. Here, we exploited differences between inbred mouse strains to identify an epithelium-intrinsic mechanism that regulates tuft cell differentiation and tunes innate type 2 immunity in the small intestine. Balb/cJ (Balb) mice had fewer intestinal
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Made to order tuft cells by an OCA-T1 isoform switch Sci. Immunol (IF 30.63) Pub Date : 2023-05-12 Xiaoli S. Wu, Christopher R. Vakoc
A genetic mechanism accounts for the variation in tuft cell abundance seen among inbred mouse strains: alternative isoforms of OCA-T1 (Oct coactivator from tuft cells 1), a recently discovered transcriptional coactivator that specifies the tuft cell lineage (see related Research Article by Nadjsombati et al. ).
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Transcriptional programming of CD4 + T RM differentiation in viral infection balances effector- and memory-associated gene expression Sci. Immunol (IF 30.63) Pub Date : 2023-05-12 Quynh P. Nguyen, Kennidy K. Takehara, Tianda Z. Deng, Shannon O’Shea, Maximilian Heeg, Kyla D. Omilusik, J. Justin Milner, Sara Quon, Matthew E. Pipkin, Jinyong Choi, Shane Crotty, Ananda W. Goldrath
After resolution of infection, T cells differentiate into long-lived memory cells that recirculate through secondary lymphoid organs or establish residence in tissues. In contrast to CD8 + tissue-resident memory T cells (T RM ), the developmental origins and transcriptional regulation of CD4 + T RM remain largely undefined. Here, we investigated the phenotypic, functional, and transcriptional profiles
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LXR signaling controls homeostatic dendritic cell maturation Sci. Immunol (IF 30.63) Pub Date : 2023-05-12 Victor Bosteels, Sandra Maréchal, Clint De Nolf, Sofie Rennen, Jonathan Maelfait, Simon J. Tavernier, Jessica Vetters, Evelien Van De Velde, Farzaneh Fayazpour, Kim Deswarte, Alexander Lamoot, Julie Van Duyse, Liesbet Martens, Cédric Bosteels, Ria Roelandt, Annelies Emmaneel, Sofie Van Gassen, Louis Boon, Gert Van Isterdael, Isabelle Guillas, Niels Vandamme, Doris Höglinger, Bruno G. De Geest, Wilfried
Dendritic cells (DCs) mature in an immunogenic or tolerogenic manner depending on the context in which an antigen is perceived, preserving the balance between immunity and tolerance. Whereas the pathways driving immunogenic maturation in response to infectious insults are well-characterized, the signals that drive tolerogenic maturation during homeostasis are still poorly understood. We found that
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"Age could not wither her…" because of her cytotoxic CD4+ T cells? Sci. Immunol (IF 30.63) Pub Date : 2023-05-05 Thomas Guy,Shiv Pillai
Cytotoxic CD4+ T cells specific for CMV cull senescent skin fibroblasts.
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Cytokinopathy with aberrant cytotoxic lymphocytes and profibrotic myeloid response in SARS-CoV-2 mRNA vaccine–associated myocarditis Sci. Immunol (IF 30.63) Pub Date : 2023-05-05 Anis Barmada, Jon Klein, Anjali Ramaswamy, Nina N. Brodsky, Jillian R. Jaycox, Hassan Sheikha, Kate M. Jones, Victoria Habet, Melissa Campbell, Tomokazu S. Sumida, Amy Kontorovich, Dusan Bogunovic, Carlos R. Oliveira, Jeremy Steele, E. Kevin Hall, Mario Pena-Hernandez, Valter Monteiro, Carolina Lucas, Aaron M. Ring, Saad B. Omer, Akiko Iwasaki, Inci Yildirim, Carrie L. Lucas
Rare immune-mediated cardiac tissue inflammation can occur after vaccination, including after SARS-CoV-2 mRNA vaccines. However, the underlying immune cellular and molecular mechanisms driving this pathology remain poorly understood. Here, we investigated a cohort of patients who developed myocarditis and/or pericarditis with elevated troponin, B-type natriuretic peptide, and C-reactive protein levels
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Unearthing the Rosetta Stone of public antibody responses Sci. Immunol (IF 30.63) Pub Date : 2023-05-05 Gianvito Masi
Comprehensive profiling of humoral responses to viruses reveals that germline-encoded V gene motifs govern the emergence of recurrent antibody epitopes across individuals.
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See no allergen, hear no allergen, speak no allergen! Sci. Immunol (IF 30.63) Pub Date : 2023-05-05 Aurore C. A. Gay, Martijn C. Nawijn
Segmental allergen challenge in allergic patients with asthma reveals a previously unknown role for monocytes in the T helper 2 (T H 2)–dependent inflammatory response, whereas in allergic controls without asthma, allergen unresponsiveness seems to be maintained through epithelial-myeloid cell cross-talk that prevents T H 2 cell activation (see related Research Article by Alladina et al. ).
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A human model of asthma exacerbation reveals transcriptional programs and cell circuits specific to allergic asthma Sci. Immunol (IF 30.63) Pub Date : 2023-05-05 Jehan Alladina, Neal P. Smith, Tristan Kooistra, Kamil Slowikowski, Isabela J. Kernin, Jacques Deguine, Henry L. Keen, Kasidet Manakongtreecheep, Jessica Tantivit, Rod A. Rahimi, Susan L. Sheng, Nhan D. Nguyen, Alexis M. Haring, Francesca L. Giacona, Lida P. Hariri, Ramnik J. Xavier, Andrew D. Luster, Alexandra-Chloé Villani, Josalyn L. Cho, Benjamin D. Medoff
Asthma is a chronic disease most commonly associated with allergy and type 2 inflammation. However, the mechanisms that link airway inflammation to the structural changes that define asthma are incompletely understood. Using a human model of allergen-induced asthma exacerbation, we compared the lower airway mucosa in allergic asthmatics and allergic non-asthmatic controls using single-cell RNA sequencing
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STING-activating nanoparticles normalize the vascular-immune interface to potentiate cancer immunotherapy Sci. Immunol (IF 30.63) Pub Date : 2023-05-05 Lihong Wang-Bishop, Blaise R. Kimmel, Verra M. Ngwa, Matthew Z. Madden, Jessalyn J. Baljon, David C. Florian, Ann Hanna, Lucinda E. Pastora, Taylor L. Sheehy, Alexander J. Kwiatkowski, Mohamed Wehbe, Xiaona Wen, Kyle W. Becker, Kyle M. Garland, Jacob A. Schulman, Daniel Shae, Deanna Edwards, Melissa M. Wolf, Rossane Delapp, Plamen P. Christov, Kathryn E. Beckermann, Justin M. Balko, W. Kimryn Rathmell
The tumor-associated vasculature imposes major structural and biochemical barriers to the infiltration of effector T cells and effective tumor control. Correlations between stimulator of interferon genes (STING) pathway activation and spontaneous T cell infiltration in human cancers led us to evaluate the effect of STING-activating nanoparticles (STANs), which are a polymersome-based platform for the
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Bcl11b sustains multipotency and restricts effector programs of intestinal-resident memory CD8 + T cells Sci. Immunol (IF 30.63) Pub Date : 2023-04-28 Eric Y. Helm, Tomas Zelenka, Valeriu B. Cismasiu, Shamima Islam, Leonardo Silvane, Beatrice Zitti, Tim D. Holmes, Theodore T. Drashansky, Alexander J. Kwiatkowski, Christine Tao, Joseph Dean, Alyssa N. Obermayer, Xianghong Chen, Benjamin G. Keselowsky, Weizhou Zhang, Zhiguang Huo, Liang Zhou, Brian S. Sheridan, Jose R. Conejo-Garcia, Timothy I. Shaw, Yenan T. Bryceson, Dorina Avram
The networks of transcription factors (TFs) that control intestinal-resident memory CD8 + T (T RM ) cells, including multipotency and effector programs, are poorly understood. In this work, we investigated the role of the TF Bcl11b in T RM cells during infection with Listeria monocytogenes using mice with post-activation, conditional deletion of Bcl11b in CD8 + T cells. Conditional deletion of Bcl11b
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Alternative splicing of GSDMB modulates killer lymphocyte–triggered pyroptosis Sci. Immunol (IF 30.63) Pub Date : 2023-04-28 Qing Kong, Shiyu Xia, Xingxin Pan, Kaixiong Ye, Zhouyihan Li, Haoyan Li, Xiaoqiang Tang, Nidhi Sahni, S. Stephen Yi, Xing Liu, Hao Wu, Michael B. Elowitz, Judy Lieberman, Zhibin Zhang
Granzyme A from killer lymphocytes cleaves gasdermin B (GSDMB) and triggers pyroptosis in targeted human tumor cells, eliciting antitumor immunity. However, GSDMB has a controversial role in pyroptosis and has been linked to both anti- and protumor functions. Here, we found that GSDMB splicing variants are functionally distinct. Cleaved N-terminal (NT) fragments of GSDMB isoforms 3 and 4 caused pyroptosis
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Tissue-resident memory T cell maintenance during antigen persistence requires both cognate antigen and interleukin-15 Sci. Immunol (IF 30.63) Pub Date : 2023-04-21 Roger Tieu, Qiang Zeng, Daqiang Zhao, Gang Zhang, Neda Feizi, Priyanka Manandhar, Amanda L. Williams, Benjamin Popp, Michelle A. Wood-Trageser, Anthony J. Demetris, J. Yun Tso, Aaron J. Johnson, Lawrence P. Kane, Khodor I. Abou-Daya, Warren D. Shlomchik, Martin H. Oberbarnscheidt, Fadi G. Lakkis
Our understanding of tissue-resident memory T (T RM ) cell biology has been largely developed from acute infection models in which antigen is cleared and sterilizing immunity is achieved. Less is known about T RM cells in the context of chronic antigen persistence and inflammation. We investigated factors that underlie T RM maintenance in a kidney transplantation model in which T RM cells drive rejection
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Encephalitis and poor neuronal death–mediated control of herpes simplex virus in human inherited RIPK3 deficiency Sci. Immunol (IF 30.63) Pub Date : 2023-04-21 Zhiyong Liu, Eduardo J. Garcia Reino, Oliver Harschnitz, Hongyan Guo, Yi-Hao Chan, Noopur V. Khobrekar, Mary L. Hasek, Kerry Dobbs, Darawan Rinchai, Marie Materna, Daniela Matuozzo, Danyel Lee, Paul Bastard, Jie Chen, Yoon Seung Lee, Seong K. Kim, Shuxiang Zhao, Param Amin, Lazaro Lorenzo, Yoann Seeleuthner, Remi Chevalier, Laure Mazzola, Claire Gay, Jean-Louis Stephan, Baptiste Milisavljevic, Soraya
Inborn errors of TLR3-dependent type I IFN immunity in cortical neurons underlie forebrain herpes simplex virus-1 (HSV-1) encephalitis (HSE) due to uncontrolled viral growth and subsequent cell death. We report an otherwise healthy patient with HSE who was compound heterozygous for nonsense (R422*) and frameshift (P493fs9*) RIPK3 variants. Receptor-interacting protein kinase 3 (RIPK3) is a ubiquitous
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Blockade of VEGFR3 signaling leads to functional impairment of dural lymphatic vessels without affecting autoimmune neuroinflammation Sci. Immunol (IF 30.63) Pub Date : 2023-04-14 Zhilin Li, Salli Antila, Harri Nurmi, Dmitri Chilov, Emilia A. Korhonen, Shentong Fang, Sinem Karaman, Britta Engelhardt, Kari Alitalo
The recent discovery of lymphatic vessels (LVs) in the dura mater, the outermost layer of meninges around the central nervous system (CNS), has opened a possibility for the development of alternative therapeutics for CNS disorders. The vascular endothelial growth factor C (VEGF-C)/VEGF receptor 3 (VEGFR3) signaling pathway is essential for the development and maintenance of dural LVs. However, its
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Metabolic challenges and interventions in CAR T cell therapy Sci. Immunol (IF 30.63) Pub Date : 2023-04-14 Jhan-Jie Peng, Limei Wang, Zhiyu Li, Cheng-Lung Ku, Ping-Chih Ho
Chimeric antigen receptor (CAR) T cells have achieved true clinical success in treating hematological malignancy patients, laying the foundation of CAR T cells as a new pillar of cancer therapy. Although these promising effects have generated strong interest in expanding the treatment of CAR T cells to solid tumors, reproducible demonstration of clinical efficacy in the setting of solid tumors has
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Human T follicular helper clones seed the germinal center–resident regulatory pool Sci. Immunol (IF 30.63) Pub Date : 2023-04-07 Carole Le Coz, Derek A. Oldridge, Ramin S. Herati, Nina De Luna, James Garifallou, Emylette Cruz Cabrera, Jonathan P. Belman, Dana Pueschl, Luisa V. Silva, Ainsley V. C. Knox, Whitney Reid, Samuel Yoon, Karen B. Zur, Steven D. Handler, Hakon Hakonarson, E. John Wherry, Michael Gonzalez, Neil Romberg
The mechanisms by which FOXP3 + T follicular regulatory (Tfr) cells simultaneously steer antibody formation toward microbe or vaccine recognition and away from self-reactivity remain incompletely understood. To explore underappreciated heterogeneity in human Tfr cell development, function, and localization, we used paired TCRVA / TCRVB sequencing to distinguish tonsillar Tfr cells that are clonally
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Computational prediction of MHC anchor locations guides neoantigen identification and prioritization Sci. Immunol (IF 30.63) Pub Date : 2023-04-07 Huiming Xia, Joshua McMichael, Michelle Becker-Hapak, Onyinyechi C. Onyeador, Rico Buchli, Ethan McClain, Patrick Pence, Suangson Supabphol, Megan M. Richters, Anamika Basu, Cody A. Ramirez, Cristina Puig-Saus, Kelsy C. Cotto, Sharon L. Freshour, Jasreet Hundal, Susanna Kiwala, S. Peter Goedegebuure, Tanner M. Johanns, Gavin P. Dunn, Antoni Ribas, Christopher A. Miller, William E. Gillanders, Todd
Neoantigens are tumor-specific peptide sequences resulting from sources such as somatic DNA mutations. Upon loading onto major histocompatibility complex (MHC) molecules, they can trigger recognition by T cells. Accurate neoantigen identification is thus critical for both designing cancer vaccines and predicting response to immunotherapies. Neoantigen identification and prioritization relies on correctly
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Identification of a broadly fibrogenic macrophage subset induced by type 3 inflammation Sci. Immunol (IF 30.63) Pub Date : 2023-04-07 Thomas Fabre, Alexander M. S. Barron, Stephen M. Christensen, Shoh Asano, Kathryn Bound, Matthew P. Lech, Marc H. Wadsworth, Xiao Chen, Chang Wang, Ju Wang, James McMahon, Franklin Schlerman, Alexis White, Kellie M. Kravarik, Andrew J. Fisher, Lee A. Borthwick, Kevin M. Hart, Neil C. Henderson, Thomas A. Wynn, Ken Dower
Macrophages are central orchestrators of the tissue response to injury, with distinct macrophage activation states playing key roles in fibrosis progression and resolution. Identifying key macrophage populations found in human fibrotic tissues could lead to new treatments for fibrosis. Here, we used human liver and lung single-cell RNA sequencing datasets to identify a subset of CD9 + TREM2 + macrophages
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The expanding family of T follicular regulatory cells Sci. Immunol (IF 30.63) Pub Date : 2023-04-07 Luis Graca, Johanne Jacobsen, Saumya Kumar
The coevolution of multiple specialized T follicular regulatory cell subsets has led to fine-tuning of human germinal center responses in providing optimal antibody production and preventing events leading to autoimmunity (see the related Research Article by Le Coz et al .).
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Celastrol suppresses humoral immune responses and autoimmunity by targeting the COMMD3/8 complex Sci. Immunol (IF 30.63) Pub Date : 2023-03-31 Taiichiro Shirai, Akiko Nakai, Emiko Ando, Jun Fujimoto, Sarah Leach, Takao Arimori, Daisuke Higo, Floris J. van Eerden, Janyerkye Tulyeu, Yu-Chen Liu, Daisuke Okuzaki, Masanori A. Murayama, Haruhiko Miyata, Kazuto Nunomura, Bangzhong Lin, Akiyoshi Tani, Atsushi Kumanogoh, Masahito Ikawa, James B. Wing, Daron M. Standley, Junichi Takagi, Kazuhiro Suzuki
Celastrol, a bioactive molecule extracted from the Tripterygium wilfordii plant, has been shown to exhibit anti-inflammatory properties. However, its mechanism of action has not been fully elucidated. Here, we show that celastrol suppresses humoral immune responses and autoimmunity by disabling a protein complex consisting of copper metabolism MURR1 domain–containing (COMMD) 3 and COMMD8 (COMMD3/8
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NK-like CD8 + γδ T cells are expanded in persistent Mycobacterium tuberculosis infection Sci. Immunol (IF 30.63) Pub Date : 2023-03-31 Roshni Roy Chowdhury, John R. Valainis, Megha Dubey, Lotta von Boehmer, Elsa Sola, Julie Wilhelmy, Jing Guo, Oliver Kask, Mane Ohanyan, Meng Sun, Huang Huang, Xianxi Huang, Patricia K. Nguyen, Thomas J. Scriba, Mark M. Davis, Sean C. Bendall, Yueh-hsiu Chien
The response of gamma delta (γδ) T cells in the acute versus chronic phases of the same infection is unclear. How γδ T cells function in acute Mycobacterium tuberculosis (Mtb) infection is well characterized, but their response during persistent Mtb infection is not well understood, even though most infections with Mtb manifest as a chronic, clinically asymptomatic state. Here, we analyze peripheral
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DNA repair mechanisms that promote insertion-deletion events during immunoglobulin gene diversification Sci. Immunol (IF 30.63) Pub Date : 2023-03-24 Qian Hao, Chuanzong Zhan, Chaoyang Lian, Simin Luo, Wenyi Cao, Binbin Wang, Xia Xie, Xiaofei Ye, Tuantuan Gui, Claudia Voena, Chiara Pighi, Yanyan Wang, Ying Tian, Xin Wang, Pengfei Dai, Yanni Cai, Xiaojing Liu, Shengqun Ouyang, Shiqi Sun, Qianwen Hu, Jun Liu, Youqiong Ye, Jingkun Zhao, Aiguo Lu, Ji-Yang Wang, Chuanxin Huang, Bing Su, Fei-Long Meng, Roberto Chiarle, Qiang Pan-Hammarström, Leng-Siew
Insertions and deletions (indels) are low-frequency deleterious genomic DNA alterations. Despite their rarity, indels are common, and insertions leading to long complementarity-determining region 3 (CDR3) are vital for antigen-binding functions in broadly neutralizing and polyreactive antibodies targeting viruses. Because of challenges in detecting indels, the mechanism that generates indels during
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The transcription factor Mef2d regulates B:T synapse–dependent GC-T FH differentiation and IL-21–mediated humoral immunity Sci. Immunol (IF 30.63) Pub Date : 2023-03-24 Ye-Ji Kim, Jeein Oh, Soohan Jung, Chan Johng Kim, Jinyong Choi, Yoon Kyung Jeon, Hyun Jik Kim, Ji-Won Kim, Chang-Hee Suh, Yoontae Lee, Sin-Hyeog Im, Shane Crotty, Youn Soo Choi
Communication between CD4 T cells and cognate B cells is key for the former to fully mature into germinal center–T follicular helper (GC-T FH ) cells and for the latter to mount a CD4 T cell–dependent humoral immune response. Although this interaction occurs in a B:T synapse–dependent manner, how CD4 T cells transcriptionally regulate B:T synapse formation remains largely unknown. Here, we report that
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Single-cell dissection of human hematopoietic reconstitution after allogeneic hematopoietic stem cell transplantation Sci. Immunol (IF 30.63) Pub Date : 2023-03-17 Yingying Huo, Linjie Wu, Aiming Pang, Qing Li, Fang Hong, Caiying Zhu, Zining Yang, Weiqian Dai, Yawei Zheng, Qianqian Meng, Jiali Sun, Shihui Ma, Linping Hu, Ping Zhu, Fang Dong, Xin Gao, Erlie Jiang, Sha Hao, Tao Cheng
Hematopoietic stem cell transplantation is an effective regenerative therapy for many malignant, inherited, or autoimmune diseases. However, our understanding of reconstituted hematopoiesis in transplant patients remains limited. Here, we uncover the reconstitution dynamics of human allogeneic hematopoietic stem and progenitor cells (HSPCs) at single-cell resolution after transplantation. Transplanted
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A mast cell–thermoregulatory neuron circuit axis regulates hypothermia in anaphylaxis Sci. Immunol (IF 30.63) Pub Date : 2023-03-17 Chunjing Bao, Ouyang Chen, Huaxin Sheng, Jeffrey Zhang, Yikai Luo, Byron W. Hayes, Han Liang, Wolfgang Liedtke, Ru-Rong Ji, Soman N. Abraham
IgE-mediated anaphylaxis is an acute life-threatening systemic reaction to allergens, including certain foods and venoms. Anaphylaxis is triggered when blood-borne allergens activate IgE-bound perivascular mast cells (MCs) throughout the body, causing an extensive systemic release of MC mediators. Through precipitating vasodilatation and vascular leakage, these mediators are believed to trigger a sharp
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Targeting the chromatin effector Pygo2 promotes cytotoxic T cell responses and overcomes immunotherapy resistance in prostate cancer Sci. Immunol (IF 30.63) Pub Date : 2023-03-10 Yini Zhu, Yun Zhao, Jiling Wen, Sheng Liu, Tianhe Huang, Ishita Hatial, Xiaoxia Peng, Hawraa Al Janabi, Gang Huang, Jackson Mittlesteadt, Michael Cheng, Atul Bhardwaj, Brandon L. Ashfeld, Kenneth R. Kao, Dean Y. Maeda, Xing Dai, Olaf Wiest, Brian S.J. Blagg, Xuemin Lu, Liang Cheng, Jun Wan, Xin Lu
The noninflamed microenvironment in prostate cancer represents a barrier to immunotherapy. Genetic alterations underlying cancer cell–intrinsic oncogenic signaling are increasingly appreciated for their role in shaping the immune landscape. Recently, we identified Pygopus 2 ( PYGO2 ) as the driver oncogene for the amplicon at 1q21.3 in prostate cancer. Here, using transgenic mouse models of metastatic
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An XBP1s–PIM-2 positive feedback loop controls IL-15–mediated survival of natural killer cells Sci. Immunol (IF 30.63) Pub Date : 2023-03-10 Shoubao Ma, Jingjing Han, Zhenlong Li, Sai Xiao, Jianying Zhang, Jiazhuo Yan, Tingting Tang, Tasha Barr, Andrew S. Kraft, Michael A. Caligiuri, Jianhua Yu
Spliced X-box–binding protein 1 (XBP1s) is an essential transcription factor downstream of interleukin-15 (IL-15) and AKT signaling, which controls cell survival and effector functions of human natural killer (NK) cells. However, the precise mechanisms, especially the downstream targets of XBP1s, remain unknown. In this study, by using XBP1 conditional knockout mice, we found that XBP1s is critical
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Fc glycoengineering of a PD-L1 antibody harnesses Fcγ receptors for increased antitumor efficacy Sci. Immunol (IF 30.63) Pub Date : 2023-03-03 Noy Cohen Saban, Adam Yalin, Tomer Landsberger, Ran Salomon, Ajjai Alva, Tali Feferman, Ido Amit, Rony Dahan
FDA-approved anti–PD-L1 monoclonal antibodies (mAbs) bear the IgG1 isotype, whose scaffolds are either wild-type (e.g., avelumab) or Fc-mutated and lacking Fcγ receptor (FcγR) engagement (e.g., atezolizumab). It is unknown whether variation in the ability of the IgG1 Fc region to engage FcγRs renders mAbs with superior therapeutic activity. In this study, we used humanized FcγR mice to study the contribution
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CD19 CAR antigen engagement mechanisms and affinity tuning Sci. Immunol (IF 30.63) Pub Date : 2023-03-03 Changhao He, Jorge Mansilla-Soto, Nandish Khanra, Mohamad Hamieh, Victor Bustos, Alice J. Paquette, Andreina Garcia Angus, Derek M. Shore, William J. Rice, George Khelashvili, Michel Sadelain, Joel R. Meyerson
Chimeric antigen receptor (CAR) T cell therapy relies on T cells that are guided by synthetic receptors to target and lyse cancer cells. CARs bind to cell surface antigens through an scFv (binder), the affinity of which is central to determining CAR T cell function and therapeutic success. CAR T cells targeting CD19 were the first to achieve marked clinical responses in patients with relapsed/refractory
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Immune checkpoint blockade induces gut microbiota translocation that augments extraintestinal antitumor immunity Sci. Immunol (IF 30.63) Pub Date : 2023-03-03 Yongbin Choi, Jake N. Lichterman, Laura A. Coughlin, Nicole Poulides, Wenling Li, Priscilla Del Valle, Suzette N. Palmer, Shuheng Gan, Jiwoong Kim, Xiaowei Zhan, Yajing Gao, Bret M. Evers, Lora V. Hooper, Chandrashekhar Pasare, Andrew Y. Koh
Gut microbiota, specifically gut bacteria, are critical for effective immune checkpoint blockade therapy (ICT) for cancer. The mechanisms by which gut microbiota augment extraintestinal anticancer immune responses, however, are largely unknown. Here, we find that ICT induces the translocation of specific endogenous gut bacteria into secondary lymphoid organs and subcutaneous melanoma tumors. Mechanistically
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Don’t FRET—Antigens in the follicle are protected from degradation Sci. Immunol (IF 30.63) Pub Date : 2023-03-03 Yujin Lee, Emily R. Siniscalco, Magdalena Kraft, Stephanie C. Eisenbarth
Low protease activity in the FDC network is crucial for intact antigen retention and has translational potential for more effective vaccination strategies.
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Plasmablasts from the past: Nostalgic B cells can’t let go Sci. Immunol (IF 30.63) Pub Date : 2023-03-03 Sarah N. Ohashi, Kevin C. O’Connor
An approach for identifying antibodies derived from distinct B cell populations demonstrates how secondary immunization responses are dominated by mature B cells generated during primary responses.
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pDC-like cells are pre-DC2 and require KLF4 to control homeostatic CD4 T cells Sci. Immunol (IF 30.63) Pub Date : 2023-02-24 Patrick Fernandes Rodrigues, Athanasios Kouklas, Grozdan Cvijetic, Nicolas Bouladoux, Mladen Mitrovic, Jigar V. Desai, Djalma S. Lima-Junior, Michail S. Lionakis, Yasmine Belkaid, Robert Ivanek, Roxane Tussiwand
Plasmacytoid dendritic cells (pDCs) have been shown to play an important role during immune responses, ranging from initial viral control through the production of type I interferons to antigen presentation. However, recent studies uncovered unexpected heterogeneity among pDCs. We identified a previously uncharacterized immune subset, referred to as pDC-like cells, that not only resembles pDCs but
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Dampening type 2 properties of group 2 innate lymphoid cells by a gammaherpesvirus infection reprograms alveolar macrophages Sci. Immunol (IF 30.63) Pub Date : 2023-02-24 Pauline Loos, Jérôme Baiwir, Céline Maquet, Justine Javaux, Rémy Sandor, François Lallemand, Thomas Marichal, Bénédicte Machiels, Laurent Gillet
Immunological dysregulation in asthma is associated with changes in exposure to microorganisms early in life. Gammaherpesviruses (γHVs), such as Epstein-Barr virus, are widespread human viruses that establish lifelong infection and profoundly shape host immunity. Using murid herpesvirus 4 (MuHV-4), a mouse γHV, we show that after infection, lung-resident and recruited group 2 innate lymphoid cells
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Inhibition of the mitochondrial pyruvate carrier simultaneously mitigates hyperinflammation and hyperglycemia in COVID-19 Sci. Immunol (IF 30.63) Pub Date : 2023-02-23 Bibo Zhu, Xiaoqin Wei, Harish Narasimhan, Wei Qian, Ruixuan Zhang, In Su Cheon, Yue Wu, Chaofan Li, Russell G. Jones, Mark H. Kaplan, Robert A. Vassallo, Thomas J. Braciale, Lindsay Somerville, Jerry R. Colca, Akhilesh Pandey, Patrick E. H. Jackson, Barbara J. Mann, Connie M. Krawczyk, Jeffrey M. Sturek, Jie Sun
The relationship between diabetes and COVID-19 is bi-directional: while individuals with diabetes and high blood glucose (hyperglycemia) are predisposed to severe COVID-19, SARS-CoV-2 infection can also cause hyperglycemia and exacerbate underlying metabolic syndrome. Therefore, interventions capable of breaking the network of SARS-CoV-2 infection, hyperglycemia, and hyper-inflammation, all factors
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IL-21R signal reprogramming cooperates with CD40 and BCR signals to select and differentiate germinal center B cells Sci. Immunol (IF 30.63) Pub Date : 2023-02-17 Wei Luo, Laura Conter, Rebecca A. Elsner, Shuchi Smita, Florian Weisel, Derrick Callahan, Shuxian Wu, Maria Chikina, Mark Shlomchik
Both B cell receptor (BCR) and CD40 signaling are rewired in germinal center (GC) B cells (GCBCs) to synergistically induce c-MYC and phosphorylated S6 ribosomal protein (p-S6), markers of positive selection. How interleukin-21 (IL-21), a key T follicular helper (T FH )–derived cytokine, affects GCBCs is unclear. Like BCR and CD40 signals, IL-21 receptor (IL-21R) plus CD40 signals also synergize to
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Immunosuppressive reprogramming of neutrophils by lung mesenchymal cells promotes breast cancer metastasis Sci. Immunol (IF 30.63) Pub Date : 2023-02-17 Zheng Gong, Qing Li, Jiayuan Shi, Peishan Li, Li Hua, Leonard D. Shultz, Guangwen Ren
Neutrophils, the most abundant innate immune cells, function as crucial regulators of the adaptive immune system in diverse pathological conditions, including metastatic cancer. However, it remains largely unknown whether their immunomodulatory functions are intrinsic or acquired within the pathological tissue environment. Here, using mouse models of metastatic breast cancer in the lungs, we show that
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Heparan sulfate regulates IL-21 bioavailability and signal strength that control germinal center B cell selection and differentiation Sci. Immunol (IF 30.63) Pub Date : 2023-02-17 Zhian Chen, Yanfang Cui, Yin Yao, Bo Liu, Joseph Yunis, Xin Gao, Naiqi Wang, Pablo F. Cañete, Zewen Kelvin Tuong, Hongjian Sun, Hao Wang, Siling Yang, Runli Wang, Yew Ann Leong, David Simon Davis, Jiahuan Qin, Kaili Liang, Jun Deng, Conan K. Wang, Yen-Hua Huang, Jonathan A. Roco, Sam Nettelfield, Huaming Zhu, Huajun Xu, Zhijia Yu, David Craik, Zheng Liu, Hai Qi, Christopher Parish, Di Yu
In antibody responses, mutated germinal center B (B GC ) cells are positively selected for reentry or differentiation. As the products from GCs, memory B cells and antibody-secreting cells (ASCs) support high-affinity and long-lasting immunity. Positive selection of B GC cells is controlled by signals received through the B cell receptor (BCR) and follicular helper T (T FH ) cell–derived signals, in
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Human IL-23 is essential for IFN-γ–dependent immunity to mycobacteria Sci. Immunol (IF 30.63) Pub Date : 2023-02-10 Quentin Philippot, Masato Ogishi, Jonathan Bohlen, Julia Puchan, Andrés Augusto Arias, Tina Nguyen, Marta Martin-Fernandez, Clement Conil, Darawan Rinchai, Mana Momenilandi, Seyed Alireza Mahdaviani, Mohammad Keramatipour, Jérémie Rosain, Rui Yang, Taushif Khan, Anna-Lena Neehus, Marie Materna, Ji Eun Han, Jessica Peel, Federico Mele, Marc Weisshaar, Sandra Jovic, Paul Bastard, Romain Lévy, Tom Le
Patients with autosomal recessive (AR) IL-12p40 or IL-12Rβ1 deficiency display Mendelian susceptibility to mycobacterial disease (MSMD) due to impaired IFN-γ production and, less commonly, chronic mucocutaneous candidiasis (CMC) due to impaired IL-17A/F production. We report six patients from four kindreds with AR IL-23R deficiency. These patients are homozygous for one of four different loss-of-function
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CD4 binding site immunogens elicit heterologous anti–HIV-1 neutralizing antibodies in transgenic and wild-type animals Sci. Immunol (IF 30.63) Pub Date : 2023-02-10 Harry B. Gristick, Harald Hartweger, Maximilian Loewe, Jelle van Schooten, Victor Ramos, Thiago Y. Oliveira, Yoshiaki Nishimura, Nicholas S. Koranda, Abigail Wall, Kai-Hui Yao, Daniel Poston, Anna Gazumyan, Marie Wiatr, Marcel Horning, Jennifer R. Keeffe, Magnus A. G. Hoffmann, Zhi Yang, Morgan E. Abernathy, Kim-Marie A. Dam, Han Gao, Priyanthi N. P. Gnanapragasam, Leesa M. Kakutani, Ana Jimena Pavlovitch-Bedzyk
Passive transfer of broadly neutralizing anti–HIV-1 antibodies (bNAbs) protects against infection, and therefore, eliciting bNAbs by vaccination is a major goal of HIV-1 vaccine efforts. bNAbs that target the CD4 binding site (CD4bs) on HIV-1 Env are among the most broadly active, but to date, responses elicited against this epitope in vaccinated animals have lacked potency and breadth. We hypothesized
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Is it bad, is it good, or is IgG4 just misunderstood? Sci. Immunol (IF 30.63) Pub Date : 2023-02-07 Shiv Pillai
Repeated doses of mRNA vaccines for COVID-19 result in increased proportions of anti-Spike antibodies of the IgG4 subclass, that are known to neutralize well and to form mixed immune complexes with IgG1 but in a pure form might be less effective than IgG1 or IgG3 antibodies in facilitating opsonization by phagocytes, complement fixation, and NK cell-dependent elimination of infected cells (see related
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Lung epithelial cell–derived C3 protects against pneumonia-induced lung injury Sci. Immunol (IF 30.63) Pub Date : 2023-02-03 Sanjaya K. Sahu, Ayşe N. Ozantürk, Devesha H. Kulkarni, Lina Ma, Ruteja A. Barve, Linus Dannull, Angel Lu, Marick Starick, Ja’Nia McPhatter, Lorena Garnica, Maxwell Sanfillipo-Burchman, Jeremy Kunen, Xiaobo Wu, Andrew E. Gelman, Steven L. Brody, John P. Atkinson, Hrishikesh S. Kulkarni
The complement component C3 is a fundamental plasma protein for host defense, produced largely by the liver. However, recent work has demonstrated the critical importance of tissue-specific C3 expression in cell survival. Here, we analyzed the effects of local versus peripheral sources of C3 expression in a model of acute bacterial pneumonia induced by Pseudomonas aeruginosa . Whereas mice with global
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Noncanonical splicing junctions between exons and transposable elements represent a source of immunogenic recurrent neo-antigens in patients with lung cancer Sci. Immunol (IF 30.63) Pub Date : 2023-02-03 Antonela Merlotti, Benjamin Sadacca, Yago A. Arribas, Mercia Ngoma, Marianne Burbage, Christel Goudot, Alexandre Houy, Ares Rocañín-Arjó, Ana Lalanne, Agathe Seguin-Givelet, Marine Lefevre, Sandrine Heurtebise-Chrétien, Blandine Baudon, Giacomo Oliveira, Damarys Loew, Montserrat Carrascal, Catherine J. Wu, Olivier Lantz, Marc-Henri Stern, Nicolas Girard, Joshua J. Waterfall, Sebastian Amigorena
Although most characterized tumor antigens are encoded by canonical transcripts (such as differentiation or tumor-testis antigens) or mutations (both driver and passenger mutations), recent results have shown that noncanonical transcripts including long noncoding RNAs and transposable elements (TEs) can also encode tumor-specific neo-antigens. Here, we investigate the presentation and immunogenicity
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Finding TB vaccine antigens: follow the TCRs Sci. Immunol (IF 30.63) Pub Date : 2023-02-03 Andrew Lichtman
TCR sequencing and analysis of predicted CDR3 structures were used to identify TCR similarity groups and the M. tuberculosis antigens they recognize that associate with infection control or progression.
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Epigenetically controlled tumor antigens derived from splice junctions between exons and transposable elements Sci. Immunol (IF 30.63) Pub Date : 2023-02-03 Marianne Burbage, Ares Rocañín-Arjó, Blandine Baudon, Yago A. Arribas, Antonela Merlotti, Derek C. Rookhuizen, Sandrine Heurtebise-Chrétien, Mengliang Ye, Alexandre Houy, Nina Burgdorf, Guadalupe Suarez, Marine Gros, Benjamin Sadacca, Montserrat Carrascal, Andrea Garmilla, Mylène Bohec, Sylvain Baulande, Bérangère Lombard, Damarys Loew, Joshua J. Waterfall, Marc-Henri Stern, Christel Goudot, Sebastian
Oncogenesis often implicates epigenetic alterations, including derepression of transposable elements (TEs) and defects in alternative splicing. Here, we explore the possibility that noncanonical splice junctions between exons and TEs represent a source of tumor-specific antigens. We show that mouse normal tissues and tumor cell lines express wide but distinct ranges of mRNA junctions between exons
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T-independent responses to polysaccharides in humans mobilize marginal zone B cells prediversified against gut bacterial antigens Sci. Immunol (IF 30.63) Pub Date : 2023-01-27 Sandra Weller, Delphine Sterlin, Tatiana Fadeev, Eva Coignard, Alba Verge de los Aires, Clara Goetz, Rémi Fritzen, Mathilde Bahuaud, Frederic Batteux, Guy Gorochov, Jean-Claude Weill, Claude-Agnès Reynaud
Marginal zone (MZ) B cells are one of the main actors of T-independent (TI) responses in mice. To identify the B cell subset(s) involved in such responses in humans, we vaccinated healthy individuals with Pneumovax, a model TI vaccine. By high-throughput repertoire sequencing of plasma cells (PCs) isolated 7 days after vaccination and of different B cell subpopulations before and after vaccination
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Human neutralizing antibodies to cold linear epitopes and subdomain 1 of the SARS-CoV-2 spike glycoprotein Sci. Immunol (IF 30.63) Pub Date : 2023-01-26 Filippo Bianchini, Virginia Crivelli, Morgan E. Abernathy, Concetta Guerra, Martin Palus, Jonathan Muri, Harold Marcotte, Antonio Piralla, Mattia Pedotti, Raoul De Gasparo, Luca Simonelli, Milos Matkovic, Chiara Toscano, Maira Biggiogero, Veronica Calvaruso, Pavel Svoboda, Tomás Cervantes Rincón, Tommaso Fava, Lucie Podešvová, Akanksha A. Shanbhag, Andrea Celoria, Jacopo Sgrignani, Michal Stefanik
Emergence of SARS-CoV-2 variants diminishes the efficacy of vaccines and antiviral monoclonal antibodies. Continued development of immunotherapies and vaccine immunogens resilient to viral evolution is therefore necessary. Using coldspot-guided antibody discovery, a screening approach that focuses on portions of the virus spike glycoprotein that are both functionally relevant and averse to change,
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A multimorphic mutation in IRF4 causes human autosomal dominant combined immunodeficiency. Sci. Immunol (IF 30.63) Pub Date : 2023-01-20 ,Oriol Fornes,Alicia Jia,Hye Sun Kuehn,Qing Min,Ulrich Pannicke,Nikolai Schleussner,Romane Thouenon,Zhijia Yu,María de Los Angeles Astbury,Catherine M Biggs,Miguel Galicchio,Jorge Alberto Garcia-Campos,Silvina Gismondi,Guadalupe Gonzalez Villarreal,Kyla J Hildebrand,Manfred Hönig,Jia Hou,Despina Moshous,Stefania Pittaluga,Xiaowen Qian,Jacob Rozmus,Ansgar S Schulz,Aidé Tamara Staines-Boone,Bijun Sun
Interferon regulatory factor 4 (IRF4) is a transcription factor (TF) and key regulator of immune cell development and function. We report a recurrent heterozygous mutation in IRF4, p.T95R, causing an autosomal dominant combined immunodeficiency (CID) in seven patients from six unrelated families. The patients exhibited profound susceptibility to opportunistic infections, notably Pneumocystis jirovecii
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Species-specific self-DNA detection mechanisms by mammalian cyclic GMP-AMP synthases Sci. Immunol (IF 30.63) Pub Date : 2023-01-20 Kenta Mosallanejad, Stephanie N. Kennedy, Kristin M. Bahleda, Kailey M. Slavik, Wen Zhou, Apurva A. Govande, Dustin C. Hancks, Philip J. Kranzusch, Jonathan C. Kagan
The mechanisms by which innate immune receptors mediate self-nonself discrimination are unclear. In this study, we found species-specific molecular determinants of self-DNA reactivity by cyclic guanosine monophosphate–adenosine monophosphate (GMP–AMP) synthase (cGAS). Human cGAS contained a catalytic domain that was intrinsically self-DNA reactive and stimulated interferon responses in diverse cell
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Silent recognition of flagellins from human gut commensal bacteria by Toll-like receptor 5 Sci. Immunol (IF 30.63) Pub Date : 2023-01-20 Sara J. Clasen, Michael E. W. Bell, Andrea Borbón, Du-Hwa Lee, Zachariah M. Henseler, Jacobo de la Cuesta-Zuluaga, Katarzyna Parys, Jun Zou, Yanling Wang, Veronika Altmannova, Nicholas D. Youngblut, John R. Weir, Andrew T. Gewirtz, Youssef Belkhadir, Ruth E. Ley
Flagellin, the protein subunit of the bacterial flagellum, stimulates the innate immune receptor Toll-like receptor 5 (TLR5) after pattern recognition or evades TLR5 through lack of recognition. This binary response fails to explain the weak agonism of flagellins from commensal bacteria, raising the question of how TLR5 response is tuned. Here, we screened abundant flagellins present in metagenomes
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B cell– and T cell–intrinsic regulation of germinal centers by thymic stromal lymphopoietin signaling Sci. Immunol (IF 30.63) Pub Date : 2023-01-20 Phillip P. Domeier, Ziaur S.M. Rahman, Steven F. Ziegler
Long-lived and high-affinity antibodies are derived from germinal center (GC) activity, but the cytokines that regulate GC function are still being identified. Here, we show that thymic stromal lymphopoietin (TSLP) signaling regulates the GC and the magnitude of antigen-specific antibody responses. Both GC B cells and T follicular helper (T FH ) cells up-regulate the expression of surface TSLP receptor
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Evading the Toll booth: How “silent” flagellins may bind yet fail to activate TLR5 Sci. Immunol (IF 30.63) Pub Date : 2023-01-20 Hannah M. Baer, Shruti Sandilya, Theodore S. Steiner
The nature of flagellin–Toll-like receptor 5 (TLR5) interactions, depending on binding to and activation of TLR5, may hold a key to the distinct differences in gut microbiome and intestinal immune function in different populations around the world (see related Research Article by Clasen et al .).
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Epithelial-intrinsic defects in TGFβR signaling drive local allergic inflammation manifesting as eosinophilic esophagitis Sci. Immunol (IF 30.63) Pub Date : 2023-01-20 Karen Laky, Jessica L. Kinard, Jenny Min Li, Ian N. Moore, Justin Lack, Elizabeth R. Fischer, Juraj Kabat, Rachel Latanich, Nicholas C. Zachos, Ajinkya R. Limkar, Katherine A. Weissler, Robert W. Thompson, Thomas A. Wynn, Harry C. Dietz, Anthony L. Guerrerio, Pamela A. Frischmeyer-Guerrerio
Allergic diseases are a global health challenge. Individuals harboring loss-of-function variants in transforming growth factor–β receptor (TGFβR) genes have an increased prevalence of allergic disorders, including eosinophilic esophagitis. Allergic diseases typically localize to mucosal barriers, implicating epithelial dysfunction as a cardinal feature of allergic disease. Here, we describe an essential
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Selective STING stimulation in dendritic cells primes antitumor T cell responses Sci. Immunol (IF 30.63) Pub Date : 2023-01-13 Bakhos Jneid, Aurore Bochnakian, Caroline Hoffmann, Fabien Delisle, Emeline Djacoto, Philémon Sirven, Jordan Denizeau, Christine Sedlik, Yohan Gerber-Ferder, Frédéric Fiore, Ramazan Akyol, Carine Brousse, Robert Kramer, Ian Walters, Sylvain Carlioz, Hélène Salmon, Bernard Malissen, Marc Dalod, Eliane Piaggio, Nicolas Manel
T cells that recognize tumor antigens are crucial for mounting antitumor immune responses. Induction of antitumor T cells in immunogenic tumors depends on STING, the intracellular innate immune receptor for cyclic guanosine monophosphate–adenosine monophosphate (cGAMP) and related cyclic dinucleotides (CDNs). However, the optimal way to leverage STING activation in nonimmunogenic tumors is still unclear