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FOXP3 exon 2 controls T reg stability and autoimmunity Sci. Immunol (IF 17.727) Pub Date : 2022-06-24 Jianguang Du, Qun Wang, Shuangshuang Yang, Si Chen, Yongyao Fu, Sabine Spath, Phillip Domeier, David Hagin, Stephanie Anover-Sombke, Maya Haouili, Sheng Liu, Jun Wan, Lei Han, Juli Liu, Lei Yang, Neel Sangani, Yujing Li, Xiongbin Lu, Sarath Chandra Janga, Mark H. Kaplan, Troy R. Torgerson, Steven F. Ziegler, Baohua Zhou
Differing from the mouse Foxp3 gene that encodes only one protein product, human FOXP3 encodes two major isoforms through alternative splicing—a longer isoform (FOXP3 FL) containing all the coding exons and a shorter isoform lacking the amino acids encoded by exon 2 (FOXP3 ΔE2). The two isoforms are naturally expressed in humans, yet their differences in controlling regulatory T cell phenotype and
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Gasdermin D–mediated release of IL-33 from senescent hepatic stellate cells promotes obesity-associated hepatocellular carcinoma Sci. Immunol (IF 17.727) Pub Date : 2022-06-24 Ryota Yamagishi, Fumitaka Kamachi, Masaru Nakamura, Shota Yamazaki, Tomonori Kamiya, Masaki Takasugi, Yi Cheng, Yoshiki Nonaka, Yoshimi Yukawa-Muto, Le Thi Thanh Thuy, Yohsuke Harada, Tatsuya Arai, Tze Mun Loo, Shin Yoshimoto, Tatsuya Ando, Masahiro Nakajima, Hayao Taguchi, Takamasa Ishikawa, Hisaya Akiba, Sachiko Miyake, Masato Kubo, Yoichiro Iwakura, Shinji Fukuda, Wei-Yu Chen, Norifumi Kawada, Alexander
Long-term senescent cells exhibit a secretome termed the senescence-associated secretory phenotype (SASP). Although the mechanisms of SASP factor induction have been intensively studied, the release mechanism and how SASP factors influence tumorigenesis in the biological context remain unclear. In this study, using a mouse model of obesity-induced hepatocellular carcinoma (HCC), we identified the release
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Antigenic cartography of SARS-CoV-2 reveals that Omicron BA.1 and BA.2 are antigenically distinct Sci. Immunol (IF 17.727) Pub Date : 2022-06-23 Anna Z. Mykytyn, Melanie Rissmann, Adinda Kok, Miruna E. Rosu, Debby Schipper, Tim I. Breugem, Petra B. van den Doel, Felicity Chandler, Theo Bestebroer, Maurice de Wit, Martin E. van Royen, Richard Molenkamp, Bas B. Oude Munnink, Rory D. de Vries, Corine GeurtsvanKessel, Derek J. Smith, Marion P. G. Koopmans, Barry Rockx, Mart M. Lamers, Ron Fouchier, Bart L. Haagmans
The emergence and rapid spread of SARS-CoV-2 variants may impact vaccine efficacy significantly. The Omicron variant termed BA.2, which differs substantially from BA.1 based on genetic sequence, is currently replacing BA.1 in several countries, but its antigenic characteristics have not yet been assessed. Here, we used antigenic cartography to quantify and visualize antigenic differences between early
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Microbial uptake in oral mucosa–draining lymph nodes leads to rapid release of cytotoxic CD8 + T cells lacking a gut-homing phenotype Sci. Immunol (IF 17.727) Pub Date : 2022-06-17 Juliana Barreto de Alburquerque, Lukas M. Altenburger, Jun Abe, Diego von Werdt, Stefanie Wissmann, Jose Martínez Magdaleno, David Francisco, Geert van Geest, Xenia Ficht, Matteo Iannacone, Remy Bruggmann, Christoph Mueller, Jens V. Stein
The gastrointestinal (GI) tract constitutes an essential barrier against ingested microbes, including potential pathogens. Although immune reactions are well studied in the lower GI tract, it remains unclear how adaptive immune responses are initiated during microbial challenge of the oral mucosa (OM), the primary site of microbial encounter in the upper GI tract. Here, we identify mandibular lymph
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Activation of CD81 + skin ILC2s by cold-sensing TRPM8 + neuron-derived signals maintains cutaneous thermal homeostasis Sci. Immunol (IF 17.727) Pub Date : 2022-06-17 Ming Xu, Chao Li, Jie Yang, Amy Ye, Liping Yan, Beng San Yeoh, Lai Shi, Yu Shin Kim, Joonsoo Kang, Matam Vijay-Kumar, Na Xiong
As the outermost barrier tissue of the body, the skin harbors a large number of innate lymphoid cells (ILCs) that help maintain local homeostasis in the face of changing environments. How skin-resident ILCs are regulated and function in local homeostatic maintenance is poorly understood. We here report the discovery of a cold-sensing neuron-initiated pathway that activates skin group 2 ILCs (ILC2s)
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Myeloid cell tropism enables MHC-E–restricted CD8 + T cell priming and vaccine efficacy by the RhCMV/SIV vaccine Sci. Immunol (IF 17.727) Pub Date : 2022-06-17 Scott G. Hansen, Meaghan H. Hancock, Daniel Malouli, Emily E. Marshall, Colette M. Hughes, Kurt T. Randall, David Morrow, Julia C. Ford, Roxanne M. Gilbride, Andrea N. Selseth, Renee Espinosa Trethewy, Lindsey M. Bishop, Kelli Oswald, Rebecca Shoemaker, Brian Berkemeier, William J. Bosche, Michael Hull, Lorna Silipino, Michael Nekorchuk, Kathleen Busman-Sahay, Jacob D. Estes, Michael K. Axthelm, Jeremy
The strain 68-1 rhesus cytomegalovirus (RhCMV)–based vaccine for simian immunodeficiency virus (SIV) can stringently protect rhesus macaques (RMs) from SIV challenge by arresting viral replication early in primary infection. This vaccine elicits unconventional SIV-specific CD8 + T cells that recognize epitopes presented by major histocompatibility complex (MHC)–II and MHC-E instead of MHC-Ia. Although
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Regional specification of oral mucosal immunity Sci. Immunol (IF 17.727) Pub Date : 2022-06-17 Drake W. Williams, George Hajishengallis, Niki M. Moutsopoulos
In this issue of Science Immunology , Barreto de Albuquerque et al. track immune responsiveness to the foodborne pathogen Listeria monocytogenes during oral infection. Their findings extend the notion of compartmentalized immunity within the gastrointestinal tract to the oral cavity and provide previously unkown insights into regional specialization of oral immunity.
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ATR-mediated CD47 and PD-L1 up-regulation restricts radiotherapy-induced immune priming and abscopal responses in colorectal cancer Sci. Immunol (IF 17.727) Pub Date : 2022-06-10 Rodney Cheng-En Hsieh, Sunil Krishnan, Ren-Chin Wu, Akash R. Boda, Arthur Liu, Michelle Winkler, Wen-Hao Hsu, Steven Hsesheng Lin, Mien-Chie Hung, Li-Chuan Chan, Krithikaa Rajkumar Bhanu, Anupallavi Srinivasamani, Ricardo Alexandre De Azevedo, Yung-Chih Chou, Ronald A. DePinho, Matthew Gubin, Eduardo Vilar, Chao Hsien Chen, Ravaen Slay, Priyamvada Jayaprakash, Shweta Mahendra Hegde, Genevieve Hartley
Radiotherapy (RT) of colorectal cancer (CRC) can prime adaptive immunity against tumor-associated antigen (TAA)–expressing CRC cells systemically. However, abscopal tumor remissions are extremely rare, and the postirradiation immune escape mechanisms in CRC remain elusive. Here, we found that irradiated CRC cells used ATR-mediated DNA repair signaling pathway to up-regulate both CD47 and PD-L1, which
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NuRD complex recruitment to Thpok mediates CD4 + T cell lineage differentiation Sci. Immunol (IF 17.727) Pub Date : 2022-06-10 Yayi Gao, Monica Zamisch, Melanie Vacchio, Laura Chopp, Thomas Ciucci, Elliott L. Paine, Gaelyn C. Lyons, Jia Nie, Qi Xiao, Ekaterina Zvezdova, Paul E. Love, Charles R. Vinson, Lisa M. Jenkins, Rémy Bosselut
Although BTB–zinc finger (BTB-ZF) transcription factors control the differentiation of multiple hematopoietic and immune lineages, how they function is poorly understood. The BTB-ZF factor Thpok controls intrathymic CD4 + T cell development and the expression of most CD4 + and CD8 + lineage genes. Here, we identify the nucleosome remodeling and deacetylase (NuRD) complex as a critical Thpok cofactor
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Clonal evolution and TCR specificity of the human T FH cell response to Plasmodium falciparum CSP Sci. Immunol (IF 17.727) Pub Date : 2022-06-10 Ilka Wahl, Anna S. Obraztsova, Julia Puchan, Rebecca Hundsdorfer, Sumana Chakravarty, B. Kim Lee Sim, Stephen L. Hoffman, Peter G. Kremsner, Benjamin Mordmüller, Hedda Wardemann
T follicular helper (T FH ) cells play a crucial role in the development of long-lived, high-quality B cell responses after infection and vaccination. However, little is known about how antigen-specific T FH cells clonally evolve in response to complex pathogens and what guides the targeting of different epitopes. Here, we assessed the cell phenotype, clonal dynamics, and T cell receptor (TCR) specificity
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Maternal gut microbiome–induced IgG regulates neonatal gut microbiome and immunity Sci. Immunol (IF 17.727) Pub Date : 2022-06-10 Katherine Z. Sanidad, Mohammed Amir, Aparna Ananthanarayanan, Anvita Singaraju, Nicholas B. Shiland, Hanna S. Hong, Nobuhiko Kamada, Naohiro Inohara, Gabriel Núñez, Melody Y. Zeng
The gut microbiome elicits antigen-specific immunoglobulin G (IgG) at steady state that cross-reacts to pathogens to confer protection against systemic infection. The role of gut microbiome–specific IgG antibodies in the development of the gut microbiome and immunity against enteric pathogens in early life, however, remains largely undefined. In this study, we show that gut microbiome–induced maternal
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Three residues in the BTB domain promote a good partnership between NuRD and Thpok Sci. Immunol (IF 17.727) Pub Date : 2022-06-10 Kazuki Okuyama, Ichiro Taniuchi
Among the BTB-ZF transcription factor family, three amino acids in the BTB domain make Thpok unique in repressing cytotoxic lineage-related genes via recruitment of the NuRD chormatin-remodeling complex (see the related Research Article by Gao et al. ).
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Selfish antibodies target auto-antigens in cancer. Sci. Immunol (IF 17.727) Pub Date : 2022-06-03 Ángel Garza Reyna,Gabriel K Griffin
Auto-antibodies against MMP14 define tumor-reactive humoral responses in ovarian cancer.
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The circadian immune system Sci. Immunol (IF 17.727) Pub Date : 2022-06-03 Chen Wang, Lydia Kay Lutes, Coline Barnoud, Christoph Scheiermann
The immune system is highly time-of-day dependent. Pioneering studies in the 1960s were the first to identify immune responses to be under a circadian control. Only in the last decade, however, have the molecular factors governing circadian immune rhythms been identified. These studies have revealed a highly complex picture of the interconnectivity of rhythmicity within immune cells with that of their
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Immune gains through brain drains Sci. Immunol (IF 17.727) Pub Date : 2022-06-03 Horacio Novaira, Asha Pillai
In a mouse model of pneumococcal meningitis, skull channels provide extravascular signaling to the skull marrow capable of initiating local marrow hematopoiesis.
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An innate IL-25–ILC2–MDSC axis creates a cancer-permissive microenvironment for Apc mutation–driven intestinal tumorigenesis Sci. Immunol (IF 17.727) Pub Date : 2022-06-03 Eric Jou, Noe Rodriguez-Rodriguez, Ana-Carolina F. Ferreira, Helen E. Jolin, Paula A. Clark, Kovilen Sawmynaden, Michelle Ko, Jane E. Murphy, Jonathan Mannion, Christopher Ward, David J. Matthews, Simon J. A. Buczacki, Andrew N. J. McKenzie
Interleukin-25 (IL-25) and group 2 innate lymphoid cells (ILC2s) defend the host against intestinal helminth infection and are associated with inappropriate allergic reactions. IL-33–activated ILC2s were previously found to augment protective tissue-specific pancreatic cancer immunity. Here, we showed that intestinal IL-25–activated ILC2s created an innate cancer-permissive microenvironment. Colorectal
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RNA exosome drives early B cell development via noncoding RNA processing mechanisms Sci. Immunol (IF 17.727) Pub Date : 2022-06-03 Brice Laffleur, Carolina R. Batista, Wanwei Zhang, Junghyun Lim, Biao Yang, Delphine Rossille, Lijing Wu, Jerson Estrella, Gerson Rothschild, Evangelos Pefanis, Uttiya Basu
B cell development is linked to successful V(D)J recombination, allowing B cell receptor expression and ultimately antibody secretion for adaptive immunity. Germline noncoding RNAs (ncRNAs) are produced at immunoglobulin (Ig) loci during V(D)J recombination, but their function and posttranscriptional regulation are incompletely understood. Patients with trichohepatoenteric syndrome, characterized by
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The mammalian SKIV2L RNA exosome is essential for early B cell development Sci. Immunol (IF 17.727) Pub Date : 2022-06-03 Kun Yang, Jie Han, Jennifer G. Gill, Jason Y. Park, Meghana N. Sathe, Jyothsna Gattineni, Tracey Wright, Christian Wysocki, M. Teresa de la Morena, Nan Yan
The SKIV2L RNA exosome is an evolutionarily conserved RNA degradation complex in the eukaryotes. Mutations in the SKIV2L gene are associated with a severe inherited disorder, trichohepatoenteric syndrome (THES), with multisystem involvement but unknown disease mechanism. Here, we reported a THES patient with SKIV2L mutations showing severe primary B cell immunodeficiency, hypogammaglobulinemia, and
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ILC2s—Bipartisan politicians in cancer Sci. Immunol (IF 17.727) Pub Date : 2022-06-03 Abderezak Zebboudj, Masataka Amisaki, Vinod P. Balachandran
Group 2 innate lymphoid cells (ILC2s) are lymphocytes that both promote and suppress antitumor immunity. Jou and colleagues now report in colorectal tumorigenesis that the cytokine interleukin-25 activates ILC2s to induce myeloid cells that suppress antitumor immunity.
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Immune memory to SARS-CoV-2 Omicron BA.1 breakthrough infections: To change the vaccine or not? Sci. Immunol (IF 17.727) Pub Date : 2022-06-02 Menno C. van Zelm
Analysis of memory B cell responses to Spike antigen after Omicron BA.1 breakthrough infections provides clues on whether “original antigenic sin” is in play.
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Omicron BA.1 breakthrough infection drives cross-variant neutralization and memory B cell formation against conserved epitopes Sci. Immunol (IF 17.727) Pub Date : 2022-06-02 Jasmin Quandt, Alexander Muik, Nadine Salisch, Bonny Gaby Lui, Sebastian Lutz, Kimberly Krüger, Ann-Kathrin Wallisch, Petra Adams-Quack, Maren Bacher, Andrew Finlayson, Orkun Ozhelvaci, Isabel Vogler, Katharina Grikscheit, Sebastian Hoehl, Udo Goetsch, Sandra Ciesek, Özlem Türeci, Ugur Sahin
Omicron is the evolutionarily most distinct SARS-CoV-2 variant of concern (VOC) to date. We report that Omicron BA.1 breakthrough infection in BNT162b2-vaccinated individuals resulted in strong neutralizing activity against Omicron BA.1, BA.2 and previous SARS-CoV-2 VOCs, but not against the Omicron sublineages BA.4 and BA.5. BA.1 breakthrough infection induced a robust recall response, primarily expanding
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Persistent CAD activity in memory CD8 + T cells supports rRNA synthesis and ribosomal biogenesis required at rechallenge Sci. Immunol (IF 17.727) Pub Date : 2022-05-27 Michael D. Claiborne, Srona Sengupta, Liang Zhao, Matthew L. Arwood, Im-Meng Sun, Jiayu Wen, Elizabeth A. Thompson, Marisa Mitchell-Flack, Marikki Laiho, Jonathan D. Powell
Memory CD8 + T cells are characterized by their ability to persist long after the initial antigen encounter and their capacity to generate a rapid recall response. Recent studies have identified a role for metabolic reprogramming and mitochondrial function in promoting the longevity of memory T cells. However, detailed mechanisms involved in promoting their rapid recall response are incompletely understood
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Rgs16 promotes antitumor CD8 + T cell exhaustion Sci. Immunol (IF 17.727) Pub Date : 2022-05-27 Nina Weisshaar, Jingxia Wu, Yanan Ming, Alaa Madi, Agnes Hotz-Wagenblatt, Sicong Ma, Alessa Mieg, Marvin Hering, Ferdinand Zettl, Kerstin Mohr, Tilo Schlimbach, Nora Ten Bosch, Franziska Hertel, Lisann Müller, Hannah Byren, Mona Wang, Helena Borgers, Mareike Munz, Lukas Schmitt, Franciscus van der Hoeven, Ulrich Kloz, Rafael Carretero, Nikolai Schleußner, Rene-Filip Jackstadt, Ilse Hofmann, Guoliang
T cells become functionally exhausted in tumors, limiting T cell–based immunotherapies. Although several transcription factors regulating the exhausted T (T ex ) cell differentiation are known, comparatively little is known about the regulators of T ex cell survival. Here, we reported that the regulator of G protein signaling 16 (Rgs-16) suppressed T ex cell survival in tumors. By performing lineage
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Intratumoral immunotherapy relies on B and T cell collaboration Sci. Immunol (IF 17.727) Pub Date : 2022-05-27 Idit Sagiv-Barfi, Debra K. Czerwinski, Tanaya Shree, Julian J. K. Lohmeyer, Ronald Levy
Antitumor T cell responses are the primary mediators of cancer immunotherapy. However, many other components of the immune system are needed for efficient T cell responses to be generated. Here, we developed a combinatorial approach where a Toll-like receptor 9 agonist (CpG) and Fc-fused IL-12 protein were injected together into just one of several tumor sites in a mouse. This combination led to body-wide
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Clostridium septicum α-toxin activates the NLRP3 inflammasome by engaging GPI-anchored proteins. Sci. Immunol (IF 17.727) Pub Date : 2022-05-20 Weidong Jing,Jordan Lo Pilato,Callum Kay,Shouya Feng,Daniel Enosi Tuipulotu,Anukriti Mathur,Cheng Shen,Chinh Ngo,Anyang Zhao,Lisa A Miosge,Sidra A Ali,Elizabeth E Gardiner,Milena M Awad,Dena Lyras,Avril A B Robertson,Nadeem O Kaakoush,Si Ming Man
Clostridium species are a group of Gram-positive bacteria that cause diseases in humans, such as food poisoning, botulism, and tetanus. Here, we analyzed 10 different Clostridium species and identified that Clostridium septicum, a pathogen that causes sepsis and gas gangrene, activates the mammalian cytosolic inflammasome complex in mice and humans. Mechanistically, we demonstrate that α-toxin secreted
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Type 2 immune predisposition results in accelerated neutrophil aging causing susceptibility to bacterial infection. Sci. Immunol (IF 17.727) Pub Date : 2022-05-20 Cecilie Egholm,Alaz Özcan,Daniel Breu,Onur Boyman
Atopic individuals show enhanced type 2 immune cell responses and a susceptibility to infections with certain bacteria and viruses. Although patients with allergic diseases harbor normal counts of circulating neutrophils, these cells exert deficient effector functions. However, the underlying mechanism of this dysregulation of neutrophils remains ill defined. Here, we find that development, aging,
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Single-cell deletion analyses show control of pro–T cell developmental speed and pathways by Tcf7, Spi1, Gata3, Bcl11a, Erg, and Bcl11b Sci. Immunol (IF 17.727) Pub Date : 2022-05-20 Wen Zhou, Fan Gao, Maile Romero-Wolf, Suin Jo, Ellen V. Rothenberg
As early T cell precursors transition from multipotentiality to T lineage commitment, they change expression of multiple transcription factors. It is unclear whether individual transcription factors directly control choices between T cell identity and some alternative fate or whether these factors mostly affect proliferation or survival during the normal commitment process. Here, we unraveled the impacts
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ZBP1-dependent inflammatory cell death, PANoptosis, and cytokine storm disrupt IFN therapeutic efficacy during coronavirus infection Sci. Immunol (IF 17.727) Pub Date : 2022-05-19 Rajendra Karki, SangJoon Lee, Raghvendra Mall, Nagakannan Pandian, Yaqiu Wang, Bhesh Raj Sharma, RK Subbarao Malireddi, Dong Yang, Sanja Trifkovic, Jacob A. Steele, Jon P. Connelly, Gella Vishwanath, Mitnala Sasikala, Duvvur Nageshwar Reddy, Peter Vogel, Shondra M. Pruett-Miller, Richard Webby, Colleen Beth Jonsson, Thirumala-Devi Kanneganti
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19), continues to cause significant morbidity and mortality in the ongoing global pandemic. Understanding the fundamental mechanisms that govern innate immune and inflammatory responses during SARS-CoV-2 infection is critical for developing effective therapeutic strategies. While
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Atypical B cells up-regulate costimulatory molecules during malaria and secrete antibodies with T follicular helper cell support Sci. Immunol (IF 17.727) Pub Date : 2022-05-13 Christine S. Hopp, Jeff Skinner, Sarah L. Anzick, Christopher M. Tipton, Mary E. Peterson, Shanping Li, Safiatou Doumbo, Kassoum Kayentao, Aissata Ongoiba, Craig Martens, Boubacar Traore, Peter D. Crompton
Several infectious and autoimmune diseases are associated with an expansion of CD21 − CD27 − atypical B cells (atBCs) that up-regulate inhibitory receptors and exhibit altered B cell receptor (BCR) signaling. The function of atBCs remains unclear, and few studies have investigated the biology of pathogen-specific atBCs during acute infection. Here, we performed longitudinal flow cytometry analyses
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Pannexin 1 drives efficient epithelial repair after tissue injury Sci. Immunol (IF 17.727) Pub Date : 2022-05-13 Christopher D. Lucas, Christopher B. Medina, Finnius A. Bruton, David A. Dorward, Michael H. Raymond, Turan Tufan, J. Iker Etchegaray, Brady Barron, Magdalena E. M. Oremek, Sanja Arandjelovic, Emily Farber, Suna Onngut-Gumuscu, Eugene Ke, Moira K. B. Whyte, Adriano G. Rossi, Kodi S. Ravichandran
Epithelial tissues such as lung and skin are exposed to the environment and therefore particularly vulnerable to damage during injury or infection. Rapid repair is therefore essential to restore function and organ homeostasis. Dysregulated epithelial tissue repair occurs in several human disease states, yet how individual cell types communicate and interact to coordinate tissue regeneration is incompletely
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BMP signaling in the intestinal epithelium drives a critical feedback loop to restrain IL-13–driven tuft cell hyperplasia Sci. Immunol (IF 17.727) Pub Date : 2022-05-13 Håvard T. Lindholm, Naveen Parmar, Claire Drurey, Marta Campillo Poveda, Pia M. Vornewald, Jenny Ostrop, Alberto Díez-Sanchez, Rick M. Maizels, Menno J. Oudhoff
The intestinal tract is a common site for various types of infections including viruses, bacteria, and helminths, each requiring specific modes of immune defense. The intestinal epithelium has a pivotal role in both immune initiation and effector stages, which are coordinated by lymphocyte cytokines such as IFNγ, IL-13, and IL-22. Here, we studied intestinal epithelial immune responses using organoid
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Recall of pre-existing cross-reactive B cell memory following Omicron BA.1 breakthrough infection Sci. Immunol (IF 17.727) Pub Date : 2022-05-12 Chengzi I. Kaku, Alan J. Bergeron, Clas Ahlm, Johan Normark, Mrunal Sakharkar, Mattias N. E. Forsell, Laura M. Walker
Understanding immune responses following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infection will facilitate the development of next-generation vaccines. Here, we profiled spike (S)-specific B cell responses following Omicron/BA.1 infection in mRNA-vaccinated donors. The acute antibody response was characterized by high levels of somatic hypermutation (SHM) and a bias
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Immune recall improves antibody durability and breadth to SARS-CoV-2 variants Sci. Immunol (IF 17.727) Pub Date : 2022-05-12 Yuezhou Chen, Pei Tong, Noah Whiteman, Ali Sanjari Moghaddam, Mehrdad Zarghami, Adam Zuiani, Shaghayegh Habibi, Avneesh Gautam, F. Keerti, Caihong Bi, Tianshu Xiao, Yongfei Cai, Bing Chen, Donna Neuberg, Duane R. Wesemann
Key features of immune memory are greater and faster antigen-specific antibody responses to repeat infection. In the setting of immune-evading viral evolution, it is important to understand how far antibody memory recognition stretches across viral variants when memory cells are recalled to action by repeat invasions. It is also important to understand how immune recall influences longevity of secreted
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Antibodies induced by ancestral SARS-CoV-2 strain that cross-neutralize variants from Alpha to Omicron BA.1 Sci. Immunol (IF 17.727) Pub Date : 2022-05-10 Ian W. Windsor, Pei Tong, Olivia Lavidor, Ali Sanjari Moghaddam, Lindsay G.A. McKay, Avneesh Gautam, Yuezhou Chen, Elizabeth A. MacDonald, Duck Kyun Yoo, Anthony Griffiths, Duane R. Wesemann, Stephen C. Harrison
Neutralizing antibodies that recognize the SARS-CoV-2 spike glycoprotein are the principal host defense against viral invasion. Variants of SARS-CoV-2 bear mutations that allow escape from neutralization by many antibodies, especially those belonging to classes widely distributed in the human population. Identifying antibodies that neutralize these variants of concern and determining their prevalence
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Chat-ty B cells talk down hematopoiesis. Sci. Immunol (IF 17.727) Pub Date : 2022-05-06 Sapheya H Elhadi,Emily R Siniscalco,Stephanie C Eisenbarth
B cells produce acetylcholine that is sensed by bone marrow stromal cells and reduces hematopoiesis.
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Targeting TLR4 during vaccination boosts MAdCAM-1 + lymphoid stromal cell activation and promotes the aged germinal center response Sci. Immunol (IF 17.727) Pub Date : 2022-05-06 Alice E. Denton, James Dooley, Isabella Cinti, Alyssa Silva-Cayetano, Sigrid Fra-Bido, Silvia Innocentin, Danika L. Hill, Edward J. Carr, Andrew N.J. McKenzie, Adrian Liston, Michelle A. Linterman
The failure to generate enduring humoral immunity after vaccination is a hallmark of advancing age. This can be attributed to a reduction in the germinal center (GC) response, which generates long-lived antibody-secreting cells that protect against (re)infection. Despite intensive investigation, the primary cellular defect underlying impaired GCs in aging has not been identified. Here, we used heterochronic
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Zbtb20 identifies and controls a thymus-derived population of regulatory T cells that play a role in intestinal homeostasis Sci. Immunol (IF 17.727) Pub Date : 2022-05-06 Agata K. Krzyzanowska, Rashade A. H. Haynes II, Damian Kovalovsky, Hsin-Ching Lin, Louis Osorio, Karen L. Edelblum, Lynn M. Corcoran, Arnold B. Rabson, Lisa K. Denzin, Derek B. Sant’Angelo
The expression of BTB-ZF transcription factors such as ThPOK in CD4 + T cells, Bcl6 in T follicular helper cells, and PLZF in natural killer T cells defines the fundamental nature and characteristics of these cells. Screening for lineage-defining BTB-ZF genes led to the discovery of a subset of T cells that expressed Zbtb20. About half of Zbtb20 + T cells expressed FoxP3, the lineage-defining transcription
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Recall of B cell memory depends on relative locations of prime and boost immunization Sci. Immunol (IF 17.727) Pub Date : 2022-05-06 Masayuki Kuraoka, Chen-Hao Yeh, Goran Bajic, Ryutaro Kotaki, Shengli Song, Ian Windsor, Stephen C. Harrison, Garnett Kelsoe
Immunization or microbial infection can establish long-term B cell memory not only systemically but also locally. Evidence has suggested that local B cell memory contributes to early local plasmacytic responses after secondary challenge. However, it is unclear whether locality of immunization plays any role in memory B cell participation in recall germinal centers (GCs), which is essential for updating
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Identity thieves: T cells steal CD20 from B cells but mark themselves for certain death Sci. Immunol (IF 17.727) Pub Date : 2022-05-06 Tomokazu S. Sumida, Kevin C. O’Connor
T cells can acquire CD20 from B cells via trogocytosis, then contribute to autoimmune neurological disease while becoming targets for therapeutically effective B cell depletion.
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Mild SARS-CoV-2 infection in rhesus macaques is associated with viral control prior to antigen-specific T cell responses in tissues Sci. Immunol (IF 17.727) Pub Date : 2022-04-29 Christine E. Nelson,Sivaranjani Namasivayam,Taylor W. Foreman,Keith D. Kauffman,Shunsuke Sakai,Danielle E. Dorosky,Nickiana E. Lora,Kelsie Brooks,E. Lake Potter,Nicole L. Garza,Bernard A. P. Lafont,Reed F. Johnson,Mario Roederer,Alan Sher,Daniela Weiskopf,Alessandro Sette,Emmie de Wit,Heather D. Hickman,Jason M. Brenchley,Laura E. Via,Daniel L. Barber,Ayan Abdi,Emmuanual K. Dayao,Joel D. Fleegle,Felipe
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily replicates in mucosal sites, and more information is needed about immune responses in infected tissues. Here, we used rhesus macaques to model protective primary immune responses in tissues during mild coronavirus disease 2019 (COVID-19). Viral RNA levels were highest on days 1 to 2 after infection and fell precipitously thereafter
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Potent TRIM21 and complement-dependent intracellular antiviral immunity requires the IgG3 hinge Sci. Immunol (IF 17.727) Pub Date : 2022-04-29 Stian Foss, Alexandra Jonsson, Maria Bottermann, Ruth Watkinson, Heidrun E. Lode, Martin B. McAdam, Terje E. Michaelsen, Inger Sandlie, Leo C. James, Jan Terje Andersen
Humans have four IgG antibody subclasses that selectively or differentially engage immune effector molecules to protect against infections. Although IgG1 has been studied in detail and is the subclass of most approved antibody therapeutics, increasing evidence indicates that IgG3 is associated with enhanced protection against pathogens. Here, we report that IgG3 has superior capacity to mediate intracellular
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Succinate dehydrogenase/complex II is critical for metabolic and epigenetic regulation of T cell proliferation and inflammation Sci. Immunol (IF 17.727) Pub Date : 2022-04-29 Xuyong Chen, Benjamin Sunkel, Meng Wang, Siwen Kang, Tingting Wang, J. N. Rashida Gnanaprakasam, Lingling Liu, Teresa A. Cassel, David A. Scott, Ana M. Muñoz-Cabello, Jose Lopez-Barneo, Jun Yang, Andrew N. Lane, Gang Xin, Benjamin Z. Stanton, Teresa W.-M. Fan, Ruoning Wang
Effective T cell–mediated immune responses require the proper allocation of metabolic resources to sustain growth, proliferation, and cytokine production. Epigenetic control of the genome also governs T cell transcriptome and T cell lineage commitment and maintenance. Cellular metabolic programs interact with epigenetic regulation by providing substrates for covalent modifications of chromatin. By
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An ACE2-blocking antibody confers broad neutralization and protection against Omicron and other SARS-CoV-2 variants of concern Sci. Immunol (IF 17.727) Pub Date : 2022-04-26 Wenjuan Du, Daniel L. Hurdiss, Dubravka Drabek, Anna Z. Mykytyn, Franziska K. Kaiser, Mariana González-Hernández, Diego Muñoz-Santos, Mart M. Lamers, Rien van Haperen, Wentao Li, Ieva Drulyte, Chunyan Wang, Isabel Sola, Federico Armando, Georg Beythien, Malgorzata Ciurkiewicz, Wolfgang Baumgärtner, Kate Guilfoyle, Tony Smits, Joline van der Lee, Frank J.M. van Kuppeveld, Geert van Amerongen, Bart L
The ongoing evolution of SARS-CoV-2 has resulted in the emergence of Omicron, which displays striking immune escape potential through mutations at key antigenic sites on the spike protein. Many of these mutations localize to the spike protein ACE2 receptor-binding domain, annulling the neutralizing activity of therapeutic antibodies that were effective against other Variants of Concern (VOCs) earlier
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SARS-CoV-2 Omicron-neutralizing memory B cells are elicited by two doses of BNT162b2 mRNA vaccine Sci. Immunol (IF 17.727) Pub Date : 2022-04-22 Ryutaro Kotaki, Yu Adachi, Saya Moriyama, Taishi Onodera, Shuetsu Fukushi, Takaki Nagakura, Keisuke Tonouchi, Kazutaka Terahara, Lin Sun, Tomohiro Takano, Ayae Nishiyama, Masaharu Shinkai, Kunihiro Oba, Fukumi Nakamura-Uchiyama, Hidefumi Shimizu, Tadaki Suzuki, Takayuki Matsumura, Masanori Isogawa, Yoshimasa Takahashi
Science Immunology, Volume 7, Issue 70, April 2022.
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Central memory T cells are the most effective precursors of resident memory T cells in human skin Sci. Immunol (IF 17.727) Pub Date : 2022-04-22 Tiago R. Matos, Ahmed Gehad, Jessica E. Teague, Beatrice Dyring-Andersen, Theresa Benezeder, Mitra Dowlatshahi, Jack Crouch, Yoshinori Watanabe, John T. O’Malley, Thomas S. Kupper, Chao Yang, Rei Watanabe, Rachael A. Clark
The circulating precursor cells that give rise to human resident memory T cells (T RM ) are poorly characterized. We used an in vitro differentiation system and human skin–grafted mice to study T RM generation from circulating human memory T cell subsets. In vitro T RM differentiation was associated with functional changes, including enhanced IL-17A production and FOXP3 expression in CD4 + T cells
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Allogeneic double-negative CAR-T cells inhibit tumor growth without off-tumor toxicities Sci. Immunol (IF 17.727) Pub Date : 2022-04-22 Daniel Vasic, Jong Bok Lee, Yuki Leung, Ismat Khatri, Yoosu Na, Daniel Abate-Daga, Li Zhang
The development of autologous chimeric antigen receptor T (CAR-T) cell therapies has revolutionized cancer treatment. Nevertheless, the delivery of CAR-T cell therapy faces challenges, including high costs, lengthy production times, and manufacturing failures. To overcome this, attempts have been made to develop allogeneic CAR-T cells using donor-derived conventional CD4 + or CD8 + T cells (T convs
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SARS-CoV-2 epitope-specific CD4 + memory T cell responses across COVID-19 disease severity and antibody durability Sci. Immunol (IF 17.727) Pub Date : 2022-04-21 Ryan W. Nelson,Yuezhou Chen,Olivia L. Venezia,Richard M Majerus,Daniel S. Shin,Mary N. Carrington,Xu G. Yu,Duane R. Wesemann,James J. Moon,Andrew D. Luster,Betelihem A. Abayneh,Patrick Allen,Galit Alter,Diane Antille,Katrina Armstrong,Alejandro Balazs,Julia Bals,Max Barbash,Yannic Bartsch,Julie Boucau,Siobhan Boyce,Joan Braley,Karen Branch,Katherine Broderick,Julia Carney,Andrew Chan,Josh Chevalier
CD4 + T cells are central to long-term immunity against viruses through the functions of T helper-1 (Th1) and T follicular helper (Tfh) cell subsets. To better understand the role of these subsets in COVID-19 immunity, we conducted a longitudinal study of SARS-CoV-2-specific CD4 + T cell and antibody responses in convalescent subjects who seroconverted during the first wave of the pandemic in Boston
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Redefining inflammatory macrophage phenotypes across stages and tissues by single-cell transcriptomics Sci. Immunol (IF 17.727) Pub Date : 2022-04-15 P’ng Loke, Jian-Da Lin
Single-cell transcriptomic data identifies major activation paths of monocyte-derived macrophages as a framework for inflammatory tissue macrophages.
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Classification of human chronic inflammatory skin disease based on single-cell immune profiling Sci. Immunol (IF 17.727) Pub Date : 2022-04-15 Yale Liu, Hao Wang, Mark Taylor, Christopher Cook, Alejandra Martínez-Berdeja, Jeffrey P. North, Paymann Harirchian, Ashley A. Hailer, Zijun Zhao, Ruby Ghadially, Roberto R. Ricardo-Gonzalez, Roy C. Grekin, Theodora M. Mauro, Esther Kim, Jaehyuk Choi, Elizabeth Purdom, Raymond J. Cho, Jeffrey B. Cheng
Inflammatory conditions represent the largest class of chronic skin disease, but the molecular dysregulation underlying many individual cases remains unclear. Single-cell RNA sequencing (scRNA-seq) has increased precision in dissecting the complex mixture of immune and stromal cell perturbations in inflammatory skin disease states. We single-cell–profiled CD45 + immune cell transcriptomes from skin
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CD45RA + CD62L − ILCs in human tissues represent a quiescent local reservoir for the generation of differentiated ILCs Sci. Immunol (IF 17.727) Pub Date : 2022-04-15 Efthymia Kokkinou, Ram Vinay Pandey, Luca Mazzurana, Irene Gutierrez-Perez, Christopher Andrew Tibbitt, Whitney Weigel, Tea Soini, Anna Carrasco, Anna Rao, Maho Nagasawa, Suzanne M. Bal, Mattias Jangard, Danielle Friberg, Ulrik Lindforss, Caroline Nordenvall, Malin Ljunggren, Staffan Haapaniemi, Åsa V. Keita, Johan Söderholm, Charlotte Hedin, Hergen Spits, Yenan T. Bryceson, Jenny Mjösberg
Innate lymphoid cells (ILCs) are highly plastic and predominantly mucosal tissue-resident cells that contribute to both homeostasis and inflammation depending on the microenvironment. The discovery of naïve-like ILCs suggests an ILC differentiation process that is akin to naïve T cell differentiation. Delineating the mechanisms that underlie ILC differentiation in tissues is crucial for understanding
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A common framework of monocyte-derived macrophage activation Sci. Immunol (IF 17.727) Pub Date : 2022-04-15 David E. Sanin, Yan Ge, Emilija Marinkovic, Agnieszka M. Kabat, Angela Castoldi, George Caputa, Katarzyna M. Grzes, Jonathan D. Curtis, Elizabeth A. Thompson, Sebastian Willenborg, Stefanie Dichtl, Susanne Reinhardt, Andreas Dahl, Erika L. Pearce, Sabine A. Eming, Alexander Gerbaulet, Axel Roers, Peter J. Murray, Edward J. Pearce
Macrophages populate every organ during homeostasis and disease, displaying features of tissue imprinting and heterogeneous activation. The disconnected picture of macrophage biology that has emerged from these observations is a barrier for integration across models or with in vitro macrophage activation paradigms. We set out to contextualize macrophage heterogeneity across mouse tissues and inflammatory
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Androgen conspires with the CD8 + T cell exhaustion program and contributes to sex bias in cancer Sci. Immunol (IF 17.727) Pub Date : 2022-04-14 Hyunwoo Kwon, Johanna M. Schafer, No-Joon Song, Satoshi Kaneko, Anqi Li, Tong Xiao, Anjun Ma, Carter Allen, Komal Das, Lei Zhou, Brian Riesenberg, Yuzhou Chang, Payton Weltge, Maria Velegraki, David Y. Oh, Lawrence Fong, Qin Ma, Debasish Sundi, Dongjun Chung, Xue Li, Zihai Li
Sex bias exists in the development and progression of non-reproductive organ cancers, but the underlying mechanisms are enigmatic. Studies so far have focused largely on sexual dimorphisms in cancer biology and socioeconomic factors. Here, we establish a role for CD8 + T cell-dependent anti-tumor immunity in mediating sex differences in tumor aggressiveness, which is driven by the gonadal androgen
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ILC killer: Qu’est-ce que c’est? Sci. Immunol (IF 17.727) Pub Date : 2022-04-08 David R. Withers, Matthew R. Hepworth
A new study published in this issue by Nixon et al . demonstrates a cytotoxic transcriptional program, characterized by granzyme C expression, that distinguishes group 1 innate lymphoid cells from classical natural killer cells across multiple tissues in mice.
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Human enteric viruses autonomously shape inflammatory bowel disease phenotype through divergent innate immunomodulation Sci. Immunol (IF 17.727) Pub Date : 2022-04-08 Fatemeh Adiliaghdam, Hajera Amatullah, Sreehaas Digumarthi, Tahnee L. Saunders, Raza-Ur Rahman, Lai Ping Wong, Ruslan Sadreyev, Lindsay Droit, Jean Paquette, Philippe Goyette, John D. Rioux, Richard Hodin, Kathie A. Mihindukulasuriya, Scott A. Handley, Kate L. Jeffrey
Altered enteric microorganisms in concert with host genetics shape inflammatory bowel disease (IBD) phenotypes. However, insight is limited to bacteria and fungi. We found that eukaryotic viruses and bacteriophages (collectively, the virome), enriched from non-IBD, noninflamed human colon resections, actively elicited atypical anti-inflammatory innate immune programs. Conversely, ulcerative colitis
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Two sides of the same coin: Protective versus pathogenic CD4 + resident memory T cells Sci. Immunol (IF 17.727) Pub Date : 2022-04-08 Anna E. Oja, René A. W. van Lier, Pleun Hombrink
The ability of the adaptive immune system to form memory is key to providing protection against secondary infections. Resident memory T cells (T RM ) are specialized T cell populations that reside within tissue sites where they await reencounter with their cognate antigen. T RM are distinct from circulating memory cells, including central and effector memory T cells, both functionally and transcriptionally
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Cytotoxic granzyme C–expressing ILC1s contribute to antitumor immunity and neonatal autoimmunity Sci. Immunol (IF 17.727) Pub Date : 2022-04-08 Briana G. Nixon, Chun Chou, Chirag Krishna, Saïda Dadi, Adam O. Michel, Andrew E. Cornish, Emily R. Kansler, Mytrang H. Do, Xinxin Wang, Kristelle J. Capistrano, Alexander Y. Rudensky, Christina S. Leslie, Ming O. Li
Innate lymphocytes are integral components of the cellular immune system that can coordinate host defense against a multitude of challenges and trigger immunopathology when dysregulated. Natural killer (NK) cells and innate lymphoid cells (ILCs) are innate immune effectors postulated to functionally mirror conventional cytotoxic T lymphocytes and helper T cells, respectively. Here, we showed that the
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Human dendritic cells in cancer Sci. Immunol (IF 17.727) Pub Date : 2022-04-01 Egle Kvedaraite, Florent Ginhoux
Dendritic cells (DCs) are professional antigen-presenting cells, orchestrating innate and adaptive immunity during infections, autoimmune diseases, and malignancies. Since the discovery of DCs almost 50 years ago, our understanding of their biology in humans has increased substantially. Here, we review both antitumor and tolerogenic DC responses in cancer and discuss lineage-specific contributions
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Multiplexed imaging mass cytometry of the chemokine milieus in melanoma characterizes features of the response to immunotherapy Sci. Immunol (IF 17.727) Pub Date : 2022-04-01 Tobias Hoch, Daniel Schulz, Nils Eling, Julia Martínez Gómez, Mitchell P. Levesque, Bernd Bodenmiller
Intratumoral immune cells are crucial for tumor control and antitumor responses during immunotherapy. Immune cell trafficking into tumors is mediated by binding of specific immune cell receptors to chemokines, a class of secreted chemotactic cytokines. To broadly characterize chemokine expression and function in melanoma, we used multiplexed mass cytometry–based imaging of protein markers and RNA transcripts
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Separation anxiety: Splitting PD-L1 from CD80 suppresses autoimmunity Sci. Immunol (IF 17.727) Pub Date : 2022-04-01 Nathan A. Bracey, Jonathan S. Maltzman
A monoclonal antibody targeting CD80 on antigen presenting cells disrupts cis-interactions with PD-L1, reviving T cell inhibitory checkpoint signaling to suppress autoimmunity.
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Spatially mapping the immune landscape of melanoma using imaging mass cytometry Sci. Immunol (IF 17.727) Pub Date : 2022-04-01 Dan Moldoveanu, LeeAnn Ramsay, Mathieu Lajoie, Luke Anderson-Trocme, Marine Lingrand, Diana Berry, Lucas J.M. Perus, Yuhong Wei, Cleber Moraes, Rached Alkallas, Shivshankari Rajkumar, Dongmei Zuo, Matthew Dankner, Eric Hongbo Xu, Nicholas R. Bertos, Hamed S. Najafabadi, Simon Gravel, Santiago Costantino, Martin J. Richer, Amanda W. Lund, Sonia V. Del Rincon, Alan Spatz, Wilson H. Miller, Rahima Jamal
Melanoma is an immunogenic cancer with a high response rate to immune checkpoint inhibitors (ICIs). It harbors a high mutation burden compared with other cancers and, as a result, has abundant tumor-infiltrating lymphocytes (TILs) within its microenvironment. However, understanding the complex interplay between the stroma, tumor cells, and distinct TIL subsets remains a substantial challenge in immune