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  • The cytoskeletal regulator HEM1 governs B cell development and prevents autoimmunity
    Sci. Immunol (IF 13.44) Pub Date : 2020-07-10
    Elisabeth Salzer, Samaneh Zoghi, Máté G. Kiss, Frieda Kage, Christina Rashkova, Stephanie Stahnke, Matthias Haimel, René Platzer, Michael Caldera, Rico Chandra Ardy, Birgit Hoeger, Jana Block, David Medgyesi, Celine Sin, Sepideh Shahkarami, Renate Kain, Vahid Ziaee, Peter Hammerl, Christoph Bock, Jörg Menche, Loïc Dupré, Johannes B. Huppa, Michael Sixt, Alexis Lomakin, Klemens Rottner, Christoph J

    The WAVE regulatory complex (WRC) is crucial for assembly of the peripheral branched actin network constituting one of the main drivers of eukaryotic cell migration. Here, we uncover an essential role of the hematopoietic-specific WRC component HEM1 for immune cell development. Germline-encoded HEM1 deficiency underlies an inborn error of immunity with systemic autoimmunity, at cellular level marked

  • Human effector T cells express TOX—Not so “TOX”ic after all
    Sci. Immunol (IF 13.44) Pub Date : 2020-07-03
    Daniel T. Utzschneider, Axel Kallies

    TOX expression is not restricted to exhausted T cells but a characteristic of all human effector CD8+ T cells.

  • TOX is expressed by exhausted and polyfunctional human effector memory CD8+ T cells
    Sci. Immunol (IF 13.44) Pub Date : 2020-07-03
    Takuya Sekine, André Perez-Potti, Son Nguyen, Jean-Baptiste Gorin, Vincent H. Wu, Emma Gostick, Sian Llewellyn-Lacey, Quirin Hammer, Sara Falck-Jones, Sindhu Vangeti, Meng Yu, Anna Smed-Sörensen, Ahmed Gaballa, Michael Uhlin, Johan K. Sandberg, Christian Brander, Piotr Nowak, Paul A. Goepfert, David A. Price, Michael R. Betts, Marcus Buggert

    CD8+ T cell exhaustion is a hallmark of many cancers and chronic infections. In mice, T cell factor 1 (TCF-1) maintains exhausted CD8+ T cell responses, whereas thymocyte selection-associated HMG box (TOX) is required for the epigenetic remodeling and survival of exhausted CD8+ T cells. However, it has remained unclear to what extent these transcription factors play analogous roles in humans. In this

  • Human antibodies neutralize enterovirus D68 and protect against infection and paralytic disease
    Sci. Immunol (IF 13.44) Pub Date : 2020-07-03
    Matthew R. Vogt, Jianing Fu, Nurgun Kose, Lauren E. Williamson, Robin Bombardi, Ian Setliff, Ivelin S. Georgiev, Thomas Klose, Michael G. Rossmann, Yury A. Bochkov, James E. Gern, Richard J. Kuhn, James E. Crowe

    Enterovirus D68 (EV-D68) causes outbreaks of respiratory illness, and there is increasing evidence that it causes outbreaks of acute flaccid myelitis (AFM). There are no licensed therapies to prevent or treat EV-D68 infection or AFM disease. We isolated a panel of EV-D68–reactive human monoclonal antibodies that recognize diverse antigenic variants from participants with prior infection. One potently

  • Let’s talk about sex
    Sci. Immunol (IF 13.44) Pub Date : 2020-07-03
    James C. Patti, Gabriel K. Griffin

    Complement gene variation drives sex biases in autoimmune disease.

  • Finding Camel-ot: A Holy Grail against pandemic SARS-CoV-2?
    Sci. Immunol (IF 13.44) Pub Date : 2020-07-03
    Deborah Soong, Rachel Leeman, Asha Pillai

    Engineered camelid antibody multimers can potently block SARS-CoV-2 viral entry.

  • Glycolipid-peptide vaccination induces liver-resident memory CD8+ T cells that protect against rodent malaria
    Sci. Immunol (IF 13.44) Pub Date : 2020-06-26
    Lauren E. Holz, Yu Cheng Chua, Maria N. de Menezes, Regan J. Anderson, Sarah L. Draper, Benjamin J. Compton, Susanna T. S. Chan, Juby Mathew, Jasmine Li, Lukasz Kedzierski, Zhongfang Wang, Lynette Beattie, Matthias H. Enders, Sonia Ghilas, Rose May, Thiago M. Steiner, Joshua Lange, Daniel Fernandez-Ruiz, Ana Maria Valencia-Hernandez, Taryn L. Osmond, Kathryn J. Farrand, Rebecca Seneviratna, Catarina

    Liver resident-memory CD8+ T cells (TRM cells) can kill liver-stage Plasmodium-infected cells and prevent malaria, but simple vaccines for generating this important immune population are lacking. Here, we report the development of a fully synthetic self-adjuvanting glycolipid-peptide conjugate vaccine designed to efficiently induce liver TRM cells. Upon cleavage in vivo, the glycolipid-peptide conjugate

  • Phenotype and kinetics of SARS-CoV-2-specific T cells in COVID-19 patients with acute respiratory distress syndrome
    Sci. Immunol (IF 13.44) Pub Date : 2020-06-26
    Daniela Weiskopf, Katharina S. Schmitz, Matthijs P. Raadsen, Alba Grifoni, Nisreen M.A. Okba, Henrik Endeman, Johannes P.C. van den Akker, Richard Molenkamp, Marion P.G. Koopmans, Eric C.M. van Gorp, Bart L. Haagmans, Rik L. de Swart, Alessandro Sette, Rory D. de Vries

    SARS-CoV-2 has been identified as the causative agent of a global outbreak of respiratory tract disease (COVID-19). In some patients the infection results in moderate to severe acute respiratory distress syndrome (ARDS), requiring invasive mechanical ventilation. High serum levels of IL-6, IL-10 and an immune hyperresponsiveness referred to as a ‘cytokine storm’ have been associated with poor clinical

  • Rate of replenishment and microenvironment contribute to the sexually dimorphic phenotype and function of peritoneal macrophages.
    Sci. Immunol (IF 13.44) Pub Date : 2020-06-19
    C C Bain,D A Gibson,N J Steers,K Boufea,P A Louwe,C Doherty,V González-Huici,R Gentek,M Magalhaes-Pinto,T Shaw,M Bajénoff,C Bénézech,S R Walmsley,D H Dockrell,P T K Saunders,N N Batada,S J Jenkins

    Macrophages reside in the body cavities where they maintain serosal homeostasis and provide immune surveillance. Peritoneal macrophages are implicated in the etiology of pathologies including peritonitis, endometriosis, and metastatic cancer; thus, understanding the factors that govern their behavior is vital. Using a combination of fate mapping techniques, we have investigated the impact of sex and

  • 3M-052, a synthetic TLR-7/8 agonist, induces durable HIV-1 envelope-specific plasma cells and humoral immunity in nonhuman primates.
    Sci. Immunol (IF 13.44) Pub Date : 2020-06-19
    Sudhir Pai Kasturi,Mohammed Ata Ur Rasheed,Colin Havenar-Daughton,Mathew Pham,Traci Legere,Zarpheen Jinnah Sher,Yevgeny Kovalenkov,Sanjeev Gumber,Jessica Y Huang,Raphael Gottardo,William Fulp,Alicia Sato,Sheetal Sawant,Sherry Stanfield-Oakley,Nicole Yates,Celia LaBranche,S Munir Alam,Georgia Tomaras,Guido Ferrari,David Montefiori,Jens Wrammert,Francois Villinger,Mark Tomai,John Vasilakos,Christopher

    A fundamental challenge in vaccinology is learning how to induce durable antibody responses. Live viral vaccines induce antibody responses that last a lifetime, but those induced with subunit vaccines wane rapidly. Studies in mice and humans have established that long-lived plasma cells (LLPCs) in the bone marrow (BM) are critical mediators of durable antibody responses. Here, we present data that

  • Ahr-Foxp3-RORγt axis controls gut homing of CD4+ T cells by regulating GPR15.
    Sci. Immunol (IF 13.44) Pub Date : 2020-06-12
    Lifeng Xiong,Joseph W Dean,Zheng Fu,Kristen N Oliff,John W Bostick,Jian Ye,Zongming E Chen,Marcus Mühlbauer,Liang Zhou

    The orphan chemoattractant receptor GPR15 is important for homing T lymphocytes to the large intestine, thereby maintaining intestinal immune homeostasis. However, the molecular mechanisms underlying the regulation of GPR15 expression remain elusive. Here, we show a central role of the aryl hydrocarbon receptor (Ahr) in promoting GPR15 expression in both mice and human, thus gut homing of T lymphocytes

  • Single-cell transcriptomic analysis of allergen-specific T cells in allergy and asthma.
    Sci. Immunol (IF 13.44) Pub Date : 2020-06-12
    Grégory Seumois,Ciro Ramírez-Suástegui,Benjamin J Schmiedel,Shu Liang,Bjoern Peters,Alessandro Sette,Pandurangan Vijayanand

    CD4+ T helper (TH) cells and regulatory T (Treg) cells that respond to common allergens play an important role in driving and dampening airway inflammation in patients with asthma. Until recently, direct, unbiased molecular analysis of allergen-reactive TH and Treg cells has not been possible. To better understand the diversity of these T cell subsets in allergy and asthma, we analyzed the single-cell

  • A singular role for interleukin-9 in the development of asthma.
    Sci. Immunol (IF 13.44) Pub Date : 2020-06-12
    Jonathan M Coquet

    Interleukin-9 expression by T helper cells marks allergic individuals who develop asthma (see the related Research Article by Seumois et al.).

  • The receptor binding domain of the viral spike protein is an immunodominant and highly specific target of antibodies in SARS-CoV-2 patients.
    Sci. Immunol (IF 13.44) Pub Date : 2020-06-11
    Lakshmanane Premkumar,Bruno Segovia-Chumbez,Ramesh Jadi,David R Martinez,Rajendra Raut,Alena Markmann,Caleb Cornaby,Luther Bartelt,Susan Weiss,Yara Park,Caitlin E Edwards,Eric Weimer,Erin M Scherer,Nadine Rouphael,Srilatha Edupuganti,Daniela Weiskopf,Longping V Tse,Yixuan J Hou,David Margolis,Alessandro Sette,Matthew H Collins,John Schmitz,Ralph S Baric,Aravinda M de Silva

    The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that first emerged in late 2019 is responsible for a pandemic of severe respiratory illness. People infected with this highly contagious virus can present with clinically inapparent, mild, or severe disease. Currently, the virus infection in individuals and at the population level is being monitored by PCR testing of symptomatic patients

  • T cell engagement of cross-presenting microglia protects the brain from a nasal virus infection.
    Sci. Immunol (IF 13.44) Pub Date : 2020-06-05
    E Ashley Moseman,Alexa C Blanchard,Debasis Nayak,Dorian B McGavern

    The neuroepithelium is a nasal barrier surface populated by olfactory sensory neurons that detect odorants in the airway and convey this information directly to the brain via axon fibers. This barrier surface is especially vulnerable to infection, yet respiratory infections rarely cause fatal encephalitis, suggesting a highly evolved immunological defense. Here, using a mouse model, we sought to understand

  • Oral epithelial IL-22/STAT3 signaling licenses IL-17-mediated immunity to oral mucosal candidiasis.
    Sci. Immunol (IF 13.44) Pub Date : 2020-06-05
    Felix E Y Aggor,Timothy J Break,Giraldina Trevejo-Nuñez,Natasha Whibley,Bianca M Coleman,Rachel D Bailey,Daniel H Kaplan,Julian R Naglik,Wei Shan,Amol C Shetty,Carrie McCracken,Scott K Durum,Partha S Biswas,Vincent M Bruno,Jay K Kolls,Michail S Lionakis,Sarah L Gaffen

    Oropharyngeal candidiasis (OPC; thrush) is an opportunistic infection caused by the commensal fungus Candida albicans. Interleukin-17 (IL-17) and IL-22 are cytokines produced by type 17 lymphocytes. Both cytokines mediate antifungal immunity yet activate quite distinct downstream signaling pathways. While much is now understood about how IL-17 promotes immunity in OPC, the activities of IL-22 are far

  • Sweet and low-autoantibodies deny oligodendrocytes their sugar fix.
    Sci. Immunol (IF 13.44) Pub Date : 2020-06-05
    Amanda L Hernandez,Kevin C O'Connor

    Pathogenic autoantibodies causing encephalopathy modify the expression of the glucose transporter in oligodendrocytes.

  • B cells: Your besT-bet against the flu.
    Sci. Immunol (IF 13.44) Pub Date : 2020-06-05
    Kenneth Zhou,Stephanie Eisenbarth

    T-bet+ memory B cells are a distinct subset that home to the spleen and produce neutralizing antibodies against influenza.

  • Inhibition of Bruton tyrosine kinase in patients with severe COVID-19.
    Sci. Immunol (IF 13.44) Pub Date : 2020-06-05
    Mark Roschewski,Michail S Lionakis,Jeff P Sharman,Joseph Roswarski,Andre Goy,M Andrew Monticelli,Michael Roshon,Stephen H Wrzesinski,Jigar V Desai,Marissa A Zarakas,Jacob Collen,Keith Rose,Ahmed Hamdy,Raquel Izumi,George W Wright,Kevin K Chung,Jose Baselga,Louis M Staudt,Wyndham H Wilson

    Patients with severe COVID-19 have a hyperinflammatory immune response suggestive of macrophage activation. Bruton tyrosine kinase (BTK) regulates macrophage signaling and activation. Acalabrutinib, a selective BTK inhibitor, was administered off-label to 19 patients hospitalized with severe COVID-19 (11 on supplemental oxygen; 8 on mechanical ventilation), 18 of whom had increasing oxygen requirements

  • IRF5 guides monocytes toward an inflammatory CD11c+ macrophage phenotype and promotes intestinal inflammation.
    Sci. Immunol (IF 13.44) Pub Date : 2020-05-22
    Alastair L Corbin,Maria Gomez-Vazquez,Dorothée L Berthold,Moustafa Attar,Isabelle C Arnold,Fiona M Powrie,Stephen N Sansom,Irina A Udalova

    Mononuclear phagocytes (MNPs) are vital for maintaining intestinal homeostasis but, in response to acute microbial stimulation, can also trigger immunopathology, accelerating recruitment of Ly6Chi monocytes to the gut. The regulators that control monocyte tissue adaptation in the gut remain poorly understood. Interferon regulatory factor 5 (IRF5) is a transcription factor previously shown to play a

  • Serology for SARS-CoV-2: Apprehensions, opportunities, and the path forward.
    Sci. Immunol (IF 13.44) Pub Date : 2020-05-19
    Juliet E Bryant,Andrew S Azman,Matthew J Ferrari,Benjamin F Arnold,Maciej F Boni,Yap Boum,Kyla Hayford,Francisco J Luquero,Michael J Mina,Isabel Rodriguez-Barraquer,Joseph T Wu,Djibril Wade,Guy Vernet,Daniel T Leung

    Serological testing for SARS-CoV-2 has enormous potential to contribute to COVID-19 pandemic response efforts. However, the required performance characteristics of antibody tests will critically depend on the use case (individual-level vs. population-level).

  • Early precursors and molecular determinants of tissue-resident memory CD8+ T lymphocytes revealed by single-cell RNA sequencing.
    Sci. Immunol (IF 13.44) Pub Date : 2020-05-15
    Nadia S Kurd,Zhaoren He,Tiani L Louis,J Justin Milner,Kyla D Omilusik,Wenhao Jin,Matthew S Tsai,Christella E Widjaja,Jad N Kanbar,Jocelyn G Olvera,Tiffani Tysl,Lauren K Quezada,Brigid S Boland,Wendy J Huang,Cornelis Murre,Ananda W Goldrath,Gene W Yeo,John T Chang

    During an immune response to microbial infection, CD8+ T cells give rise to distinct classes of cellular progeny that coordinately mediate clearance of the pathogen and provide long-lasting protection against reinfection, including a subset of noncirculating tissue-resident memory (TRM) cells that mediate potent protection within nonlymphoid tissues. Here, we used single-cell RNA sequencing to examine

  • TMPRSS2 and TMPRSS4 promote SARS-CoV-2 infection of human small intestinal enterocytes.
    Sci. Immunol (IF 13.44) Pub Date : 2020-05-13
    Ruochen Zang,Maria Florencia Gomez Castro,Broc T McCune,Qiru Zeng,Paul W Rothlauf,Naomi M Sonnek,Zhuoming Liu,Kevin F Brulois,Xin Wang,Harry B Greenberg,Michael S Diamond,Matthew A Ciorba,Sean P J Whelan,Siyuan Ding

    Gastrointestinal symptoms and fecal shedding of SARS-CoV-2 RNA are frequently observed in COVID-19 patients. However, it is unclear whether SARS-CoV-2 replicates in the human intestine and contributes to possible fecal-oral transmission. Here, we report productive infection of SARS-CoV-2 in ACE2+ mature enterocytes in human small intestinal enteroids. Expression of two mucosa-specific serine proteases

  • Divergent T follicular helper cell requirement for IgA and IgE production to peanut during allergic sensitization.
    Sci. Immunol (IF 13.44) Pub Date : 2020-05-08
    Biyan Zhang,Elise Liu,Jake A Gertie,Julie Joseph,Lan Xu,Elisha Y Pinker,Daniel A Waizman,Jason Catanzaro,Kedir Hussen Hamza,Katharina Lahl,Uthaman Gowthaman,Stephanie C Eisenbarth

    Immunoglobulin A (IgA) is the dominant antibody isotype in the gut and has been shown to regulate microbiota. Mucosal IgA is also widely believed to prevent food allergens from penetrating the gut lining. Even though recent work has elucidated how bacteria-reactive IgA is induced, little is known about how IgA to food antigens is regulated. Although IgA is presumed to be induced in a healthy gut at

  • HiJAKing SARS-CoV-2? The potential role of JAK inhibitors in the management of COVID-19.
    Sci. Immunol (IF 13.44) Pub Date : 2020-05-08
    Francesca Romana Spinelli,Fabrizio Conti,Massimo Gadina

    JAK kinase inhibitors are being investigated as a way of managing cytokine storm in severe COVID-19 patients.

  • Sestrins teach old T cells new tricks.
    Sci. Immunol (IF 13.44) Pub Date : 2020-05-01
    Jonathan S Maltzman

    Sestrin proteins dampen TCR signaling and induce antigen-independent natural killer-like cytotoxicity in highly differentiated CD8 T cells.

  • A respiratory syncytial virus (RSV) F protein nanoparticle vaccine focuses antibody responses to a conserved neutralization domain.
    Sci. Immunol (IF 13.44) Pub Date : 2020-05-01
    Kurt A Swanson,Jennifer N Rainho-Tomko,Zachary P Williams,Lilibeth Lanza,Michael Peredelchuk,Michael Kishko,Vincent Pavot,Judith Alamares-Sapuay,Haritha Adhikarla,Sankalp Gupta,Sudha Chivukula,Scott Gallichan,Linong Zhang,Nicholas Jackson,Heesik Yoon,Darin Edwards,Chih-Jen Wei,Gary J Nabel

    A stabilized form of the respiratory syncytial virus (RSV) fusion (F) protein has been explored as a vaccine to prevent viral infection because it presents several potent neutralizing epitopes. Here, we used a structure-based rational design to optimize antigen presentation and focus antibody (Ab) responses to key epitopes on the pre-fusion (pre-F) protein. This protein was fused to ferritin nanoparticles

  • Regulatory T cells in skin injury: At the crossroads of tolerance and tissue repair.
    Sci. Immunol (IF 13.44) Pub Date : 2020-05-01
    Ian C Boothby,Jarish N Cohen,Michael D Rosenblum

    Skin injury is a highly inflammatory process that is carefully regulated to mitigate tissue damage and allow for proper barrier repair. Regulatory T cells (Tregs) are crucial coordinators of the immune response to injury in several organs. Here, we review the emerging role of Tregs in facilitating skin repair after injury. We focus on recently discovered interactions between lymphocytes and nonhematopoietic

  • IL-23 and IL-2 activation of STAT5 is required for optimal IL-22 production in ILC3s during colitis.
    Sci. Immunol (IF 13.44) Pub Date : 2020-04-24
    David Bauché,Barbara Joyce-Shaikh,Julie Fong,Alejandro V Villarino,Karin S Ku,Renu Jain,Yu-Chi Lee,Lakshmanan Annamalai,Jennifer H Yearley,Daniel J Cua

    Signal transducer and activator of transcription (STAT) proteins have critical roles in the development and function of immune cells. STAT signaling is often dysregulated in patients with inflammatory bowel disease (IBD), suggesting the importance of STAT regulation during the disease process. Moreover, genetic alterations in STAT3 and STAT5 (e.g., deletions, mutations, and single-nucleotide polymorphisms)

  • Gut-resident CX3CR1hi macrophages induce tertiary lymphoid structures and IgA response in situ.
    Sci. Immunol (IF 13.44) Pub Date : 2020-04-10
    Balázs Koscsó,Sravya Kurapati,Richard R Rodrigues,Jelena Nedjic,Kavitha Gowda,Changsik Shin,Chetna Soni,Azree Zaffran Ashraf,Indira Purushothaman,Maryknoll Palisoc,Sulei Xu,Haoyu Sun,Sathi Babu Chodisetti,Eugene Lin,Matthias Mack,Yuka Imamura Kawasawa,Pingnian He,Ziaur S M Rahman,Iannis Aifantis,Natalia Shulzhenko,Andrey Morgun,Milena Bogunovic

    Intestinal mononuclear phagocytes (MPs) are composed of heterogeneous dendritic cell (DC) and macrophage subsets necessary for the initiation of immune response and control of inflammation. Although MPs in the normal intestine have been extensively studied, the heterogeneity and function of inflammatory MPs remain poorly defined. We performed phenotypical, transcriptional, and functional analyses of

  • IFN-III is selectively produced by cDC1 and predicts good clinical outcome in breast cancer.
    Sci. Immunol (IF 13.44) Pub Date : 2020-04-17
    Margaux Hubert,Elisa Gobbini,Coline Couillault,Thien-Phong Vu Manh,Anne-Claire Doffin,Justine Berthet,Céline Rodriguez,Vincent Ollion,Janice Kielbassa,Christophe Sajous,Isabelle Treilleux,Olivier Tredan,Bertrand Dubois,Marc Dalod,Nathalie Bendriss-Vermare,Christophe Caux,Jenny Valladeau-Guilemond

    Dendritic cells play a key role in the orchestration of antitumor immune responses. The cDC1 (conventional dendritic cell 1) subset has been shown to be essential for antitumor responses and response to immunotherapy, but its precise role in humans is largely unexplored. Using a multidisciplinary approach, we demonstrate that human cDC1 play an important role in the antitumor immune response through

  • Salivary gland macrophages and tissue-resident CD8+ T cells cooperate for homeostatic organ surveillance.
    Sci. Immunol (IF 13.44) Pub Date : 2020-04-03
    Bettina Stolp,Flavian Thelen,Xenia Ficht,Lukas M Altenburger,Nora Ruef,V V G Krishna Inavalli,Philipp Germann,Nicolas Page,Federica Moalli,Andrea Raimondi,Kirsten A Keyser,S Morteza Seyed Jafari,Francesca Barone,Matthias S Dettmer,Doron Merkler,Matteo Iannacone,James Sharpe,Christoph Schlapbach,Oliver T Fackler,U Valentin Nägerl,Jens V Stein

    It is well established that tissue macrophages and tissue-resident memory CD8+ T cells (TRM) play important roles for pathogen sensing and rapid protection of barrier tissues. In contrast, the mechanisms by which these two cell types cooperate for homeostatic organ surveillance after clearance of infections is poorly understood. Here, we used intravital imaging to show that TRM dynamically followed

  • M2-like, dermal macrophages are maintained via IL-4/CCL24–mediated cooperative interaction with eosinophils in cutaneous leishmaniasis
    Sci. Immunol (IF 13.44) Pub Date : 2020-04-10
    Sang Hun Lee, Mariana M. Chaves, Olena Kamenyeva, Pedro H. Gazzinelli-Guimaraes, Byunghyun Kang, Gabriela Pessenda, Katiuska Passelli, Fabienne Tacchini-Cottier, Juraj Kabat, Elizabeth A. Jacobsen, Thomas B. Nutman, David L. Sacks

    Tissue-resident macrophages (TRMs) maintain tissue homeostasis, but they can also provide a replicative niche for intracellular pathogens such as Leishmania. How dermal TRMs proliferate and maintain their M2 properties even in the strong TH1 environment of the L. major infected dermis is not clear. Here, we show that, in infected mice lacking IL-4/13 from eosinophils, dermal TRMs shifted to a proinflammatory

  • Learning from our immunological history: What can SARS-CoV teach us about SARS-CoV-2?
    Sci. Immunol (IF 13.44) Pub Date : 2020-04-03
    Sarah E Henrickson

    Many strategies are being deployed to rapidly uncover targetable mechanisms of infection for SARS-CoV-2, and Hoffman et al exploit our understanding and immunological experience with SARS-CoV in our global race to understand, mitigate, and eventually prevent COVID-19.

  • Sex drives Tregs into fat
    Sci. Immunol (IF 13.44) Pub Date : 2020-04-03
    Ireneusz Habrylo, Michael D. Rosenblum

    Androgens promote inflammation in visceral adipose tissue (VAT), leading to the expansion of a distinct IL-33 producing stromal population and recruitment of Tregs.

  • Organ-specific isoform selection of fatty acid–binding proteins in tissue-resident lymphocytes
    Sci. Immunol (IF 13.44) Pub Date : 2020-04-03
    H. Frizzell, R. Fonseca, S. N. Christo, M. Evrard, S. Cruz-Gomez, N. G. Zanluqui, B. von Scheidt, D. Freestone, S. L. Park, H. E. G. McWilliam, J. A. Villadangos, F. R. Carbone, L. K. Mackay

    Tissue-resident memory T (TRM) cells exist throughout the body, where they are poised to mediate local immune responses. Although studies have defined a common mechanism of residency independent of location, there is likely to be a level of specialization that adapts TRM cells to their given tissue of lodgment. It has been shown that TRM cells in the skin rely on the uptake of exogenous fatty acids

  • MAP4K4 negatively regulates CD8 T cell–mediated antitumor and antiviral immunity
    Sci. Immunol (IF 13.44) Pub Date : 2020-03-27
    Emel Esen, Ismail Sergin, Rajiv Jesudason, Patricia Himmels, Joshua D. Webster, Hua Zhang, Min Xu, Robert Piskol, Erin McNamara, Stephen Gould, Aude-Hélène Capietto, Lélia Delamarre, Kevin Walsh, Weilan Ye

    During cytotoxic T cell activation, lymphocyte function-associated antigen–1 (LFA-1) engages its ligands on antigen-presenting cells (APCs) or target cells to enhance T cell priming or lytic activity. Inhibiting LFA-1 dampens T cell–dependent symptoms in inflammation, autoimmune diseases, and graft-versus-host disease. However, the therapeutic potential of augmenting LFA-1 function is less explored

  • Identification of a nerve-associated, lung-resident interstitial macrophage subset with distinct localization and immunoregulatory properties
    Sci. Immunol (IF 13.44) Pub Date : 2020-03-27
    Basak B. Ural, Stephen T. Yeung, Payal Damani-Yokota, Joseph C. Devlin, Maren de Vries, Paola Vera-Licona, Tasleem Samji, Catherine M. Sawai, Geunhyo Jang, Oriana A. Perez, Quynh Pham, Leigh Maher, P'ng Loke, Meike Dittmann, Boris Reizis, Kamal M. Khanna

    Tissue-resident macrophages are a diverse population of cells that perform specialized functions including sustaining tissue homeostasis and tissue surveillance. Here, we report an interstitial subset of CD169+ lung-resident macrophages that are transcriptionally and developmentally distinct from alveolar macrophages (AMs). They are primarily localized around the airways and are found in close proximity

  • Lymph node stromal CCL2 limits antibody responses
    Sci. Immunol (IF 13.44) Pub Date : 2020-03-20
    Dragos C. Dasoveanu, Hyeung Ju Park, Catherine L. Ly, William D. Shipman, Susan Chyou, Varsha Kumar, David Tarlinton, Burkhard Ludewig, Babak J. Mehrara, Theresa T. Lu

    Nonhematopoietic stromal cells in lymph nodes such as fibroblastic reticular cells (FRCs) can support the survival of plasmablasts and plasma cells [together, antibody-forming cells (AFCs)]. However, a regulatory function for the stromal compartment in AFC accumulation has not been appreciated. Here, we show that chemokine ligand 2 (CCL2)–expressing stromal cells limit AFC survival. FRCs express high

  • NK cells mediate clearance of CD8+ T cell-resistant tumors in response to STING agonists.
    Sci. Immunol (IF 13.44) Pub Date : 2020-03-20
    Christopher J Nicolai,Natalie Wolf,I-Chang Chang,Georgia Kirn,Assaf Marcus,Chudi O Ndubaku,Sarah M McWhirter,David H Raulet

    Several immunotherapy approaches that mobilize CD8+ T cell responses stimulate tumor rejection, and some, such as checkpoint blockade, have been approved for several cancer indications and show impressive increases in patient survival. However, tumors may evade CD8+ T cell recognition via loss of MHC molecules or because they contain few or no neoantigens. Therefore, approaches are needed to combat

  • Cytidine deaminase 2 is required for VLRB antibody gene assembly in lampreys
    Sci. Immunol (IF 13.44) Pub Date : 2020-03-13
    Ryo Morimoto, Connor P. O’Meara, Stephen J. Holland, Inês Trancoso, Ahmed Souissi, Michael Schorpp, Danièle Vassaux, Norimasa Iwanami, Orlando B. Giorgetti, Guillaume Evanno, Thomas Boehm

    The antibodies of jawless vertebrates consist of leucine-rich repeat arrays encoded by somatically assembled VLRB genes. It is unknown how the incomplete germline VLRB loci are converted into functional antibody genes during B lymphocyte development in lampreys. In Lampetra planeri larvae lacking the cytidine deaminase CDA2 gene, VLRB assembly fails, whereas the T lineage–associated VLRA and VLRC antigen

  • Absence of MHC class II on cDC1 dendritic cells triggers fatal autoimmunity to a cross-presented self-antigen
    Sci. Immunol (IF 13.44) Pub Date : 2020-03-13
    Christian Wohn, Valentin Le Guen, Odessa Voluzan, Frédéric Fiore, Sandrine Henri, Bernard Malissen

    Conventional dendritic cells expressing the XCR1 chemokine receptor (cDC1s) excel at cross-presentation. Here, we developed and used a mouse model in which a Cre recombinase is expressed under the control of the Xcr1 gene while preserving XCR1 expression. We used it to generate mice with conditional deletion of MHC class II (MHCII) molecules on cDC1s. By preventing cDC1s to receive suppressive regulatory

  • Heat shocks T cells down a path to disease.
    Sci. Immunol (IF 13.44) Pub Date : 2020-03-06
    Andrew H Lichtman

    Febrile temperatures enhance differentiation of CD4+ T cells into pathogenic TH17 cells that contribute to autoimmune disease.

  • Long-lived T follicular helper cells retain plasticity and help sustain humoral immunity.
    Sci. Immunol (IF 13.44) Pub Date : 2020-03-06
    Marco Künzli,David Schreiner,Tamara C Pereboom,Nivedya Swarnalekha,Ludivine C Litzler,Jonas Lötscher,Yusuf I Ertuna,Julien Roux,Florian Geier,Roman P Jakob,Timm Maier,Christoph Hess,Justin J Taylor,Carolyn G King

    CD4+ memory T cells play an important role in protective immunity and are a key target in vaccine development. Many studies have focused on T central memory (Tcm) cells, whereas the existence and functional significance of long-lived T follicular helper (Tfh) cells are controversial. Here, we show that Tfh cells are highly susceptible to NAD-induced cell death (NICD) during isolation from tissues,

  • P2X7R: The Achilles heel of follicular helper memory T cells.
    Sci. Immunol (IF 13.44) Pub Date : 2020-03-06
    Jeffrey C Nolz

    Protecting TFH memory CD4+ T cells from NAD-induced cell death reveals both their longevity and plasticity (see related Research Article by Künzli et al.).

  • Origins and clonal convergence of gastrointestinal IgE+ B cells in human peanut allergy
    Sci. Immunol (IF 13.44) Pub Date : 2020-03-06
    Ramona A. Hoh, Shilpa A. Joshi, Ji-Yeun Lee, Brock A. Martin, Sushama Varma, Shirley Kwok, Sandra C. A. Nielsen, Parastu Nejad, Emily Haraguchi, Priya S. Dixit, Swetha V. Shutthanandan, Krishna M. Roskin, Wenming Zhang, Dana Tupa, Bryan J. Bunning, Monali Manohar, Robert Tibshirani, Nielsen Q. Fernandez-Becker, Neeraja Kambham, Robert B. West, Robert G. Hamilton, Mindy Tsai, Stephen J. Galli, Rebecca

    B cells in human food allergy have been studied predominantly in the blood. Little is known about IgE+ B cells or plasma cells in tissues exposed to dietary antigens. We characterized IgE+ clones in blood, stomach, duodenum, and esophagus of 19 peanut-allergic patients, using high-throughput DNA sequencing. IgE+ cells in allergic patients are enriched in stomach and duodenum, and have a plasma cell

  • PAX1 is essential for development and function of the human thymus.
    Sci. Immunol (IF 13.44) Pub Date : 2020-02-28
    Yasuhiro Yamazaki,Raul Urrutia,Luis M Franco,Silvia Giliani,Kejian Zhang,Anas M Alazami,A Kerry Dobbs,Stefania Masneri,Avni Joshi,Francisco Otaizo-Carrasquero,Timothy G Myers,Sundar Ganesan,Maria Pia Bondioni,Mai Lan Ho,Catherine Marks,Huda Alajlan,Reem W Mohammed,Fanggeng Zou,C Alexander Valencia,Alexandra H Filipovich,Fabio Facchetti,Bertrand Boisson,Chiara Azzari,Bander K Al-Saud,Hamoud Al-Mousa

    We investigated the molecular and cellular basis of severe combined immunodeficiency (SCID) in six patients with otofaciocervical syndrome type 2 who failed to attain T cell reconstitution after allogeneic hematopoietic stem cell transplantation, despite successful engraftment in three of them. We identified rare biallelic PAX1 rare variants in all patients. We demonstrated that these mutant PAX1 proteins

  • Tumor neoantigenicity assessment with CSiN score incorporates clonality and immunogenicity to predict immunotherapy outcomes.
    Sci. Immunol (IF 13.44) Pub Date : 2020-02-21
    Tianshi Lu,Shidan Wang,Lin Xu,Qinbo Zhou,Nirmish Singla,Jianjun Gao,Subrata Manna,Laurentiu Pop,Zhiqun Xie,Mingyi Chen,Jason J Luke,James Brugarolas,Raquibul Hannan,Tao Wang

    Lack of responsiveness to checkpoint inhibitors is a central problem in the modern era of cancer immunotherapy. Tumor neoantigens are critical targets of the host antitumor immune response, and their presence correlates with the efficacy of immunotherapy treatment. Many studies involving assessment of tumor neoantigens principally focus on total neoantigen load, which simplistically treats all neoantigens

  • Defining the emergence of myeloid-derived suppressor cells in breast cancer using single-cell transcriptomics.
    Sci. Immunol (IF 13.44) Pub Date : 2020-02-21
    Hamad Alshetaiwi,Nicholas Pervolarakis,Laura Lynn McIntyre,Dennis Ma,Quy Nguyen,Jan Akara Rath,Kevin Nee,Grace Hernandez,Katrina Evans,Leona Torosian,Anushka Silva,Craig Walsh,Kai Kessenbrock

    Myeloid-derived suppressor cells (MDSCs) are innate immune cells that acquire the capacity to suppress adaptive immune responses during cancer. It remains elusive how MDSCs differ from their normal myeloid counterparts, which limits our ability to specifically detect and therapeutically target MDSCs during cancer. Here, we sought to determine the molecular features of breast cancer-associated MDSCs

  • A key role for IL-13 signaling via the type 2 IL-4 receptor in experimental atopic dermatitis.
    Sci. Immunol (IF 13.44) Pub Date : 2020-02-14
    Almog Bitton,Shmuel Avlas,Hadar Reichman,Michal Itan,Danielle Karo-Atar,Nurit P Azouz,Perri Rozenberg,Yael Diesendruck,Limor Nahary,Marc E Rothenberg,Itai Benhar,Ariel Munitz

    IL-13 and IL-4 are potent mediators of type 2-associated inflammation such as those found in atopic dermatitis (AD). IL-4 shares overlapping biological functions with IL-13, a finding that is mainly explained by their ability to signal via the type 2 IL-4 receptor (R), which is composed of IL-4Rα in association with IL-13Rα1. Nonetheless, the role of the type 2 IL-4R in AD remains to be clearly defined

  • Increased islet antigen-specific regulatory and effector CD4+ T cells in healthy individuals with the type 1 diabetes-protective haplotype.
    Sci. Immunol (IF 13.44) Pub Date : 2020-02-14
    Xiaomin Wen,Junbao Yang,Eddie James,I-Ting Chow,Helena Reijonen,William W Kwok

    The DRB1*15:01-DQB1*06:02 (DR1501-DQ6) haplotype is linked to dominant protection from type 1 diabetes, but the cellular mechanism for this association is unclear. To address this question, we identified multiple DR1501- and DQ6-restricted glutamate decarboxylase 65 (GAD65) and islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP)-specific T cell epitopes. Three of the DR1501/DQ6-restricted

  • Winning with the B team?
    Sci. Immunol (IF 13.44) Pub Date : 2020-02-07
    Shiv Pillai,Faisal Alsufyani

    The accumulation of B cells and tertiary lymphoid organs in metastatic melanoma patients receiving checkpoint blockade therapy was associated with long-term survival.

  • Kill shot: Flu vaccine is a stone cold cancer killer.
    Sci. Immunol (IF 13.44) Pub Date : 2020-02-07
    Rachael A Clark

    Injection of seasonal influenza vaccine into tumors enhances local and systemic anti-cancer immunity and sensitizes previously resistant tumors to immune checkpoint therapy.

  • Specialization of mucosal immunoglobulins in pathogen control and microbiota homeostasis occurred early in vertebrate evolution.
    Sci. Immunol (IF 13.44) Pub Date : 2020-02-07
    Zhen Xu,Fumio Takizawa,Elisa Casadei,Yasuhiro Shibasaki,Yang Ding,Thomas J C Sauters,Yongyao Yu,Irene Salinas,J Oriol Sunyer

    Although mammalian secretory immunoglobulin A (sIgA) targets mucosal pathogens for elimination, its interaction with the microbiota also enables commensal colonization and homeostasis. This paradoxical requirement in the control of pathogens versus microbiota raised the question of whether mucosal (secretory) Igs (sIgs) evolved primarily to protect mucosal surfaces from pathogens or to maintain microbiome

  • Noncoding RNA transcription alters chromosomal topology to promote isotype-specific class switch recombination.
    Sci. Immunol (IF 13.44) Pub Date : 2020-02-07
    Gerson Rothschild,Wanwei Zhang,Junghyun Lim,Pankaj Kumar Giri,Brice Laffleur,Yiyun Chen,Mingyan Fang,Yuling Chen,Lekha Nair,Zhi-Ping Liu,Haiteng Deng,Lennart Hammarström,Jiguang Wang,Uttiya Basu

    B cells undergo two types of genomic alterations to increase antibody diversity: introduction of point mutations into immunoglobulin heavy- and light-chain (IgH and IgL) variable regions by somatic hypermutation (SHM) and alteration of antibody effector functions by changing the expressed IgH constant region exons through IgH class switch recombination (CSR). SHM and CSR require the B cell-specific

  • Blockade of EGFR improves responsiveness to PD-1 blockade in EGFR-mutated non-small cell lung cancer.
    Sci. Immunol (IF 13.44) Pub Date : 2020-01-31
    Eri Sugiyama,Yosuke Togashi,Yoshiko Takeuchi,Sayoko Shinya,Yasuko Tada,Keisuke Kataoka,Kenta Tane,Eiichi Sato,Genichiro Ishii,Koichi Goto,Yasushi Shintani,Meinoshin Okumura,Masahiro Tsuboi,Hiroyoshi Nishikawa

    The clinical efficacy of anti-PD-1 (programmed cell death-1) monoclonal antibody (mAb) against cancers with oncogenic driver gene mutations, which often harbor a low tumor mutation burden, is variable, suggesting different contributions of each driver mutation to immune responses. Here, we investigated the immunological phenotypes in the tumor microenvironment (TME) of epidermal growth factor receptor

  • Technical comment on "Synovial fibroblast-neutrophil interactions promote pathogenic adaptive immunity in rheumatoid arthritis".
    Sci. Immunol (IF 13.44) Pub Date : 2020-01-31
    A J Salinger,M L Dubuke,C Carmona-Rivera,A J Maurais,S A Shaffer,E Weerapana,P R Thompson,M J Kaplan

    Reassessment of citrullinome cargo in neutrophil extracellular traps confirms the presence of citrullinated peptides.

  • 更新日期:2020-01-31
  • Mutual inhibition between Prkd2 and Bcl6 controls T follicular helper cell differentiation.
    Sci. Immunol (IF 13.44) Pub Date : 2020-01-24
    Takuma Misawa,Jeffrey A SoRelle,Jin Huk Choi,Tao Yue,Kuan-Wen Wang,William McAlpine,Jianhui Wang,Aijie Liu,Koichi Tabeta,Emre E Turer,Bret Evers,Evan Nair-Gill,Subhajit Poddar,Lijing Su,Feiya Ou,Liyang Yu,Jamie Russell,Sara Ludwig,Xiaoming Zhan,Sara Hildebrand,Xiaohong Li,Miao Tang,Anne R Murray,Eva Marie Y Moresco,Bruce Beutler

    T follicular helper cells (TFH) participate in germinal center (GC) development and are necessary for B cell production of high-affinity, isotype-switched antibodies. In a forward genetic screen, we identified a missense mutation in Prkd2, encoding the serine/threonine kinase protein kinase D2, which caused elevated titers of immunoglobulin E (IgE) in the serum. Subsequent analysis of serum antibodies

  • Human DNA-PK activates a STING-independent DNA sensing pathway.
    Sci. Immunol (IF 13.44) Pub Date : 2020-01-24
    Katelyn Burleigh,Joanna H Maltbaek,Stephanie Cambier,Richard Green,Michael Gale,Richard C James,Daniel B Stetson

    Detection of intracellular DNA by the cGAS-STING pathway activates a type I interferon-mediated innate immune response that protects from virus infection. Whether there are additional DNA sensing pathways, and how such pathways might function, remains controversial. We show here that humans-but not laboratory mice-have a second, potent, STING-independent DNA sensing pathway (SIDSP). We identify human

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