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  • Severely ill COVID-19 patients display impaired exhaustion features in SARS-CoV-2-reactive CD8+ T cells
    Sci. Immunol (IF 13.44) Pub Date : 2021-01-21
    Anthony Kusnadi, Ciro Ramírez-Suástegui, Vicente Fajardo, Serena J Chee, Benjamin J Meckiff, Hayley Simon, Emanuela Pelosi, Grégory Seumois, Ferhat Ay, Pandurangan Vijayanand, Christian H Ottensmeier

    The molecular properties of CD8+ T cells that respond to SARS-CoV-2 infection are not fully known. Here, we report on the single-cell transcriptomes of >80,000 virus-reactive CD8+ T cells, obtained using a modified Antigen-Reactive T cell Enrichment (ARTE) assay, from 39 COVID-19 patients and 10 healthy subjects. COVID-19 patients segregated into two groups based on whether the dominant CD8+ T cell

    更新日期:2021-01-22
  • Inhibitory signaling sustains a distinct early memory CD8+ T cell precursor that is resistant to DNA damage
    Sci. Immunol (IF 13.44) Pub Date : 2021-01-15
    Jonathan B. Johnnidis, Yuki Muroyama, Shin Foong Ngiow, Zeyu Chen, Sasikanth Manne, Zhangying Cai, Shufei Song, Jesse M. Platt, Jason M. Schenkel, Mohamed Abdel-Hakeem, Jean-Christophe Beltra, Allison R. Greenplate, Mohammed-Alkhatim A. Ali, Kito Nzingha, Josephine R. Giles, Christelle Harly, John Attanasio, Kristen E. Pauken, Bertram Bengsch, Michael A. Paley, Vesselin T. Tomov, Makoto Kurachi, Dario

    The developmental origins of memory T cells remain incompletely understood. During the expansion phase of acute viral infection, we identified a distinct subset of virus-specific CD8+ T cells that possessed distinct characteristics including expression of CD62L, T cell factor 1 (TCF-1), and Eomesodermin; relative quiescence; expression of activation markers; and features of limited effector differentiation

    更新日期:2021-01-15
  • PD-1 blockade exacerbates Mycobacterium tuberculosis infection in rhesus macaques
    Sci. Immunol (IF 13.44) Pub Date : 2021-01-15
    Keith D. Kauffman, Shunsuke Sakai, Nickiana E. Lora, Sivaranjani Namasivayam, Paul J. Baker, Olena Kamenyeva, Taylor W. Foreman, Christine E. Nelson, Deivide Oliveira-de-Souza, Caian L. Vinhaes, Ziv Yaniv, Cecilia S. Lindestam Arleham, Alessandro Sette, Gordon J. Freeman, Rashida Moore, NIAID/DIR Tuberculosis Imaging Program, Alan Sher, Katrin D. Mayer-Barber, Bruno B. Andrade, Juraj Kabat, Laura E

    Boosting immune cell function by targeting the coinhibitory receptor PD-1 may have applications in the treatment of chronic infections. Here, we examine the role of PD-1 during Mycobacterium tuberculosis (Mtb) infection of rhesus macaques. Animals treated with anti–PD-1 monoclonal antibody developed worse disease and higher granuloma bacterial loads compared with isotype control–treated monkeys. PD-1

    更新日期:2021-01-15
  • TRH cells, helpers making an impact in their local community
    Sci. Immunol (IF 13.44) Pub Date : 2021-01-08
    Stefan A. Schattgen, Paul G. Thomas

    T resident helper cells (TRH), a T cell subset with follicular helper and resident memory properties, regulate B cell responses in nonlymphoid organs (see the related Research Articles by Swarnalekha et al. and Son et al.).

    更新日期:2021-01-10
  • Killing the buzz: NK cells in the aged brain
    Sci. Immunol (IF 13.44) Pub Date : 2021-01-08
    Rachael A. Clark

    Senescent neuroblasts activate NK cells in the dentate gyrus of the aged brain, leading to neuronal destruction that impairs cognition.

    更新日期:2021-01-10
  • T resident helper cells promote humoral responses in the lung
    Sci. Immunol (IF 13.44) Pub Date : 2021-01-08
    Nivedya Swarnalekha, David Schreiner, Ludivine C. Litzler, Saadia Iftikhar, Daniel Kirchmeier, Marco Künzli, Young Min Son, Jie Sun, Etori Aguiar Moreira, Carolyn G. King

    Influenza is a deadly and costly infectious disease, even during flu seasons when an effective vaccine has been developed. To improve vaccines against respiratory viruses, a better understanding of the immune response at the site of infection is crucial. After influenza infection, clonally expanded T cells take up permanent residence in the lung, poised to rapidly respond to subsequent infection. Here

    更新日期:2021-01-10
  • Tissue-resident CD4+ T helper cells assist the development of protective respiratory B and CD8+ T cell memory responses
    Sci. Immunol (IF 13.44) Pub Date : 2021-01-08
    Young Min Son, In Su Cheon, Yue Wu, Chaofan Li, Zheng Wang, Xiaochen Gao, Yao Chen, Yoshimasa Takahashi, Yang-Xin Fu, Alexander L. Dent, Mark H. Kaplan, Justin J. Taylor, Weiguo Cui, Jie Sun

    Much remains unknown about the roles of CD4+ T helper cells in shaping localized memory B cell and CD8+ T cell immunity in the mucosal tissues. Here, we report that lung T helper cells provide local assistance for the optimal development of tissue-resident memory B and CD8+ T cells after the resolution of primary influenza virus infection. We have identified a population of T cells in the lung that

    更新日期:2021-01-10
  • Enhanced IL-36R signaling promotes barrier impairment and inflammation in skin and intestine
    Sci. Immunol (IF 13.44) Pub Date : 2020-12-18
    Zaruhi Hovhannisyan, Nengyin Liu, Sara Khalil-Aguero, Casandra Panea, Jeffrey VanValkenburgh, Ruoyu Zhang, Wei Keat Lim, Yu Bai, Wen Fury, Tammy Huang, Elena Garnova, Jeanette Fairhurst, Jee Kim, Smita Aryal, Dharani Ajithdoss, Adelekan Oyejide, Maria del Pilar Molina-Portela, Hock E, William Poueymirou, Nicole Stokes Oristian, Susannah Brydges, Xia Liu, William Olson, George Yancopoulos, Andrew J

    Deficiency in interleukin-36R (IL-36R) antagonist caused by loss-of-function mutations in IL-36RN leads to DITRA (deficiency of IL-36 receptor antagonist), a rare inflammatory human disease that belongs to a subgroup of generalized pustular psoriasis (GPP). We report a functional genetic mouse model of DITRA with enhanced IL-36R signaling analogous to that observed in patients with DITRA, which provides

    更新日期:2020-12-24
  • Discordant neutralizing antibody and T cell responses in asymptomatic and mild SARS-CoV-2 infection
    Sci. Immunol (IF 13.44) Pub Date : 2020-12-23
    Catherine J. Reynolds, Leo Swadling, Joseph M. Gibbons, Corinna Pade, Melanie P. Jensen, Mariana O. Diniz, Nathalie M. Schmidt, David K. Butler, Oliver E. Amin, Sasha N. L. Bailey, Sam M. Murray, Franziska P. Pieper, Stephen Taylor, Jessica Jones, Meleri Jones, Wing-Yiu Jason Lee, Joshua Rosenheim, Aneesh Chandran, George Joy, Cecilia Di Genova, Nigel Temperton, Jonathan Lambourne, Teresa Cutino-Moguel

    Understanding the nature of immunity following mild/asymptomatic infection with SARS-CoV-2 is crucial to controlling the pandemic. We analyzed T cell and neutralizing antibody responses in 136 healthcare workers (HCW) 16-18 weeks after United Kingdom lockdown, 76 of whom had mild/asymptomatic SARS-CoV-2 infection captured by serial sampling. Neutralizing antibodies (nAb) were present in 89% of previously

    更新日期:2020-12-24
  • Rapid generation of durable B cell memory to SARS-CoV-2 spike and nucleocapsid proteins in COVID-19 and convalescence
    Sci. Immunol (IF 13.44) Pub Date : 2020-12-22
    Gemma E. Hartley, Emily S.J. Edwards, Pei M. Aui, Nirupama Varese, Stephanie Stojanovic, James McMahon, Anton Y. Peleg, Irene Boo, Heidi E. Drummer, P. Mark Hogarth, Robyn E. O’Hehir, Menno C. van Zelm

    Lasting immunity following SARS-CoV-2 infection is questioned because serum antibodies decline in convalescence. However, functional immunity is mediated by long-lived memory T and B (Bmem) cells. Therefore, we generated fluorescently-labeled tetramers of the spike receptor binding domain (RBD) and nucleocapsid protein (NCP) to determine the longevity and immunophenotype of SARS-CoV-2-specific Bmem

    更新日期:2020-12-24
  • Autophagy protects tumors from T cell–mediated cytotoxicity via inhibition of TNFα-induced apoptosis
    Sci. Immunol (IF 13.44) Pub Date : 2020-12-18
    Tara M. Young, Claudia Reyes, Elizabeth Pasnikowski, Carla Castanaro, Chung Wong, Corinne E. Decker, Joyce Chiu, Hang Song, Yi Wei, Yu Bai, Brian Zambrowicz, Gavin Thurston, Christopher Daly

    Although T cell checkpoint inhibitors have transformed the treatment of cancer, the molecular determinants of tumor cell sensitivity to T cell–mediated killing need further elucidation. Here, we describe a mouse genome–scale CRISPR knockout screen that identifies tumor cell TNFα signaling as an important component of T cell–induced apoptosis, with NF-κB signaling and autophagy as major protective mechanisms

    更新日期:2020-12-24
  • Defects in LC3B2 and ATG4A underlie HSV2 meningitis and reveal a critical role for autophagy in antiviral defense in humans
    Sci. Immunol (IF 13.44) Pub Date : 2020-12-11
    Alon Schneider Hait, David Olagnier, Vanessa Sancho-Shimizu, Kristian Alsbjerg Skipper, Marie Helleberg, Simon Muller Larsen, Chiranjeevi Bodda, Liviu Ionut Moldovan, Fanghui Ren, Nanna-Sophie Brinck Andersen, Michelle M. Thomsen, Mette Ratzer Freytag, Sathya Darmalinggam, Isobel Parkes, Darshana D. Kadekar, Stine Hess Rahbek, Demi van der Horst, Lasse Sommer Kristensen, Kristina Eriksson, Jørgen Kjems

    Recurrent herpesvirus infections can manifest in different forms of disease, including cold sores, genital herpes, and encephalitis. There is an incomplete understanding of the genetic and immunological factors conferring susceptibility to recurrent herpes simplex virus 2 (HSV2) infection in the central nervous system (CNS). Here, we describe two adult patients with recurrent HSV2 lymphocytic Mollaret’s

    更新日期:2020-12-12
  • CD4+ T cell activation and concomitant mTOR metabolic inhibition can ablate microbiota-specific memory cells and prevent colitis
    Sci. Immunol (IF 13.44) Pub Date : 2020-12-11
    Qing Zhao, Lennard W. Duck, Fengyuan Huang, Katie L. Alexander, Craig L. Maynard, Peter J. Mannon, Charles O. Elson

    Microbiota-reactive CD4+ T memory (TM) cells are generated during intestinal infections and inflammation, and can revert to pathogenic CD4+ T effector (TE) cells, resulting in chronicity of inflammatory bowel disease (IBD). Unlike TE cells, TM cells have a low rate of metabolism unless they are activated by reencountering cognate antigen. Here, we show that the combination of cell activation and metabolic

    更新日期:2020-12-12
  • Defining the features and duration of antibody responses to SARS-CoV-2 infection associated with disease severity and outcome
    Sci. Immunol (IF 13.44) Pub Date : 2020-12-07
    Katharina Röltgen, Abigail E. Powell, Oliver F. Wirz, Bryan A. Stevens, Catherine A. Hogan, Javaria Najeeb, Molly Hunter, Hannah Wang, Malaya K. Sahoo, ChunHong Huang, Fumiko Yamamoto, Monali Manohar, Justin Manalac, Ana R. Otrelo-Cardoso, Tho D. Pham, Arjun Rustagi, Angela J. Rogers, Nigam H. Shah, Catherine A. Blish, Jennifer R. Cochran, Theodore S. Jardetzky, James L. Zehnder, Taia T. Wang, Balasubramanian

    SARS-CoV-2-specific antibodies, particularly those preventing viral spike receptor binding domain (RBD) interaction with host angiotensin-converting enzyme 2 (ACE2) receptor, can neutralize the virus. It is, however, unknown which features of the serological response may affect clinical outcomes of COVID-19 patients. We analyzed 983 longitudinal plasma samples from 79 hospitalized COVID-19 patients

    更新日期:2020-12-08
  • Lighting a fire on the reef
    Sci. Immunol (IF 13.44) Pub Date : 2020-12-04
    Zhibin Zhang, Judy Lieberman

    Coral gasdermin E is cleaved by activated caspase-3 to induce pyroptosis, a form of inflammatory programmed cell death, in response to a bacterial pathogen (see the related Research Article by Jiang et al.).

    更新日期:2020-12-05
  • Coral gasdermin triggers pyroptosis
    Sci. Immunol (IF 13.44) Pub Date : 2020-12-04
    Shuai Jiang, Zhi Zhou, Yuanyuan Sun, Tengfei Zhang, Li Sun

    Gasdermins are executioners of the inflammatory cell death pathway pyroptosis that has so far been studied exclusively in vertebrates. In this study, we identified gasdermin E (GSDME) homologs in several invertebrate species including corals. We report that coral GSDME was cleaved by caspase 3 at two sites, yielding two active isoforms of GSDME N-terminal domain that were capable of inducing pyroptosis

    更新日期:2020-12-05
  • BATF regulates innate lymphoid cell hematopoiesis and homeostasis
    Sci. Immunol (IF 13.44) Pub Date : 2020-12-04
    Qingyang Liu, Myung H. Kim, Leon Friesen, Chang H. Kim

    Early hematopoietic progenitors undergo sophisticated developmental processes to become committed innate lymphoid cell (ILC) progenitors and ultimately mature ILC subsets in the periphery. Basic leucine zipper ATF-like transcription factor (Batf) plays important roles in lymphocyte biology. We report here that Batf regulates the production of bone marrow ILC progenitors and maintenance of peripheral

    更新日期:2020-12-05
  • B careful: Humoral responses and COVID-19 severity
    Sci. Immunol (IF 13.44) Pub Date : 2020-12-04
    Hani Fanous, Angela Guerrero-Pena, Asha Pillai

    Neutralizing antibody responses to SARS-CoV-2, though often of limited longevity, have generally been assumed to be protective against COVID-19 disease.

    更新日期:2020-12-05
  • A cytokine to remember me by
    Sci. Immunol (IF 13.44) Pub Date : 2020-12-04
    Aya Halawi, Gabriel K. Griffin

    Cohesin restrains cytokine-induced transcriptional memory.

    更新日期:2020-12-05
  • Shiga toxin suppresses noncanonical inflammasome responses to cytosolic LPS
    Sci. Immunol (IF 13.44) Pub Date : 2020-11-27
    Morena S. Havira, Atri Ta, Puja Kumari, Chengliang Wang, Ashley J. Russo, Jianbin Ruan, Vijay A. Rathinam, Sivapriya Kailasan Vanaja

    Inflammatory caspase–dependent cytosolic lipopolysaccharide (LPS) sensing is a critical arm of host defense against bacteria. How pathogens overcome this pathway to establish infections is largely unknown. Enterohemorrhagic Escherichia coli (EHEC) is a clinically important human pathogen causing hemorrhagic colitis and hemolytic uremic syndrome. We found that a bacteriophage-encoded virulence factor

    更新日期:2020-11-27
  • Human innate lymphoid cell precursors express CD48 that modulates ILC differentiation through 2B4 signaling
    Sci. Immunol (IF 13.44) Pub Date : 2020-11-20
    Dejene M. Tufa, Ashley M. Yingst, George Devon Trahan, Tyler Shank, Dallas Jones, Seonhui Shim, Jessica Lake, Kevin Winkler, Laura Cobb, Renee Woods, Kenneth Jones, Michael R. Verneris

    Innate lymphoid cells (ILCs) develop from common lymphoid progenitors (CLPs), which further differentiate into the common ILC progenitor (CILP) that can give rise to both ILCs and natural killer (NK) cells. Murine ILC intermediates have recently been characterized, but the human counterparts and their developmental trajectories have not yet been identified, largely due to the lack of homologous surface

    更新日期:2020-11-21
  • Gut microbiota–specific IgA+ B cells traffic to the CNS in active multiple sclerosis
    Sci. Immunol (IF 13.44) Pub Date : 2020-11-20
    Anne-Katrin Pröbstel, Xiaoyuan Zhou, Ryan Baumann, Sven Wischnewski, Michael Kutza, Olga L. Rojas, Katrin Sellrie, Antje Bischof, Kicheol Kim, Akshaya Ramesh, Ravi Dandekar, Ariele L. Greenfield, Ryan D. Schubert, Jordan E. Bisanz, Stephanie Vistnes, Khashayar Khaleghi, James Landefeld, Gina Kirkish, Friederike Liesche-Starnecker, Valeria Ramaglia, Sneha Singh, Edwina B. Tran, Patrick Barba, Kelsey

    Changes in gut microbiota composition and a diverse role of B cells have recently been implicated in multiple sclerosis (MS), a central nervous system (CNS) autoimmune disease. Immunoglobulin A (IgA) is a key regulator at the mucosal interface. However, whether gut microbiota shape IgA responses and what role IgA+ cells have in neuroinflammation are unknown. Here, we identify IgA-bound taxa in MS and

    更新日期:2020-11-21
  • The known unknowns of T cell immunity to COVID-19
    Sci. Immunol (IF 13.44) Pub Date : 2020-11-18
    Annika C. Karlsson, Marion Humbert, Marcus Buggert

    Tremendous progress has been made in understanding the role of T cell immunity in acute and convalescent COVID-19 infection. Here we shed light on the “known unknowns” of pre-existing and acquired T cell responses in relation to acute and convalescent SARS-CoV-2 infection.

    更新日期:2020-11-18
  • Type I interferons drive the maturation of human DC3s with a distinct costimulatory profile characterized by high GITRL
    Sci. Immunol (IF 13.44) Pub Date : 2020-11-13
    Melanie Girard, Jaclyn C. Law, Maria I. Edilova, Tania H. Watts

    Human mononuclear phagocytes comprise specialized subsets of dendritic cells (DCs) and monocytes, but how these subsets individually regulate expression of the molecular signals involved in T cell costimulation is incompletely understood. Here, we used multiparameter flow cytometry and CITE-sequencing to investigate the cell type–specific responses of human peripheral blood DC and monocyte subsets

    更新日期:2020-11-15
  • Cellular context of IL-33 expression dictates impact on anti-helminth immunity
    Sci. Immunol (IF 13.44) Pub Date : 2020-11-13
    Li-Yin Hung, Yukinori Tanaka, Karl Herbine, Christopher Pastore, Brenal Singh, Annabel Ferguson, Nisha Vora, Bonnie Douglas, Kelly Zullo, Edward M. Behrens, Tiffany Li Hui Tan, Michael A. Kohanski, Paul Bryce, Cailu Lin, Taku Kambayashi, Danielle R. Reed, Breann L. Brown, Noam A. Cohen, De’Broski R. Herbert

    Interleukin-33 (IL-33) is a pleiotropic cytokine that can promote type 2 inflammation but also drives immunoregulation through Foxp3+Treg expansion. How IL-33 is exported from cells to serve this dual role in immunosuppression and inflammation remains unclear. Here, we demonstrate that the biological consequences of IL-33 activity are dictated by its cellular source. Whereas IL-33 derived from epithelial

    更新日期:2020-11-15
  • Tissue-resident CD8+ T cells drive age-associated chronic lung sequelae after viral pneumonia
    Sci. Immunol (IF 13.44) Pub Date : 2020-11-06
    Nick P. Goplen, Yue Wu, Young Min Son, Chaofan Li, Zheng Wang, In Su Cheon, Li Jiang, Bibo Zhu, Katayoun Ayasoufi, Eduardo N. Chini, Aaron J. Johnson, Robert Vassallo, Andrew H. Limper, Nu Zhang, Jie Sun

    Lower respiratory viral infections, such as influenza virus and severe acute respiratory syndrome coronavirus 2 infections, often cause severe viral pneumonia in aged individuals. Here, we report that influenza viral pneumonia leads to chronic nonresolving lung pathology and exacerbated accumulation of CD8+ tissue-resident memory T cells (TRM) in the respiratory tract of aged hosts. TRM cell accumulation

    更新日期:2020-11-09
  • Torn between type 1 and type 2 immunity
    Sci. Immunol (IF 13.44) Pub Date : 2020-11-06
    Xiangyun Yin, Stephanie C. Eisenbarth

    DOCK8 uncovers a link between cell integrity and TH2 skewing.

    更新日期:2020-11-09
  • Two mAbs take a stab at influenza's NActive site
    Sci. Immunol (IF 13.44) Pub Date : 2020-11-06
    Minh C. Pham, Kevin C. O’Connor

    Two human-derived recombinant mAbs specific for IBV bind the neuraminidase active site by emulating the enzymatic substrate, which results in broad protection.

    更新日期:2020-11-09
  • T cell factor 1: A master regulator of the T cell response in disease
    Sci. Immunol (IF 13.44) Pub Date : 2020-11-06
    Giulia Escobar, Davide Mangani, Ana C. Anderson

    Recent advances have redefined a role for T cell factor 1 (TCF1) that goes beyond T cell development and T memory formation and encompasses new functions in the regulation of T cell biology. Here, we discuss the multifaceted and context-dependent role of TCF1 in peripheral T cells, particularly during disease-induced inflammatory states such as autoimmunity, cancer, and chronic infections. Understanding

    更新日期:2020-11-09
  • Persistent STAT5 activation reprograms the epigenetic landscape in CD4+ T cells to drive polyfunctionality and antitumor immunity
    Sci. Immunol (IF 13.44) Pub Date : 2020-10-30
    Zhi-Chun Ding, Huidong Shi, Nada S. Aboelella, Kateryna Fesenkova, Eun-Jeong Park, Zhuoqi Liu, Lirong Pei, Jiaqi Li, Richard A. McIndoe, Hongyan Xu, Gary A. Piazza, Bruce R. Blazar, David H. Munn, Gang Zhou

    The presence of polyfunctional CD4+ T cells is often associated with favorable antitumor immunity. We report here that persistent activation of signal transducer and activator of transcription 5 (STAT5) in tumor-specific CD4+ T cells drives the development of polyfunctional T cells. We showed that ectopic expression of a constitutively active form of murine STAT5A (CASTAT5) enabled tumor-specific CD4+

    更新日期:2020-11-02
  • Itaconate controls the severity of pulmonary fibrosis
    Sci. Immunol (IF 13.44) Pub Date : 2020-10-23
    Patricia P. Ogger, Gesa J. Albers, Richard J. Hewitt, Brendan J. O’Sullivan, Joseph E. Powell, Emily Calamita, Poonam Ghai, Simone A. Walker, Peter McErlean, Peter Saunders, Shaun Kingston, Philip L. Molyneaux, John M. Halket, Robert Gray, Daniel C. Chambers, Toby M. Maher, Clare M. Lloyd, Adam J. Byrne

    Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease in which airway macrophages (AMs) play a key role. Itaconate has emerged as a mediator of macrophage function, but its role during fibrosis is unknown. Here, we reveal that itaconate is an endogenous antifibrotic factor in the lung. Itaconate levels are reduced in bronchoalveolar lavage, and itaconate-synthesizing cis-aconitate decarboxylase

    更新日期:2020-10-28
  • A distinct GM-CSF+ T helper cell subset requires T-bet to adopt a TH1 phenotype and promote neuroinflammation
    Sci. Immunol (IF 13.44) Pub Date : 2020-10-23
    Javad Rasouli, Giacomo Casella, Satoshi Yoshimura, Weifeng Zhang, Dan Xiao, James Garifallou, Michael V. Gonzalez, Alice Wiedeman, Anna Kus, Elisabeth R. Mari, Paolo Fortina, Hakon Hakonarson, S. Alice Long, Guang-Xian Zhang, Bogoljub Ciric, Abdolmohamad Rostami

    Elevation of granulocyte-macrophage colony-stimulating factor (GM-CSF)–producing T helper (TH) cells has been associated with several autoimmune diseases, suggesting a potential role in the pathogenesis of autoimmunity. However, the identity of GM-CSF–producing TH cells has not been closely examined. Using single-cell RNA sequencing and high-dimensional single-cell mass cytometry, we identified eight

    更新日期:2020-10-28
  • Microglial autophagy–associated phagocytosis is essential for recovery from neuroinflammation
    Sci. Immunol (IF 13.44) Pub Date : 2020-10-16
    Rasmus Berglund, Andre Ortlieb Guerreiro-Cacais, Milena Z. Adzemovic, Manuel Zeitelhofer, Harald Lund, Ewoud Ewing, Sabrina Ruhrmann, Erik Nutma, Roham Parsa, Melanie Thessen-Hedreul, Sandra Amor, Robert A. Harris, Tomas Olsson, Maja Jagodic

    Multiple sclerosis (MS) is a leading cause of incurable progressive disability in young adults caused by inflammation and neurodegeneration in the central nervous system (CNS). The capacity of microglia to clear tissue debris is essential for maintaining and restoring CNS homeostasis. This capacity diminishes with age, and age strongly associates with MS disease progression, although the underlying

    更新日期:2020-10-17
  • A discrete subset of epigenetically primed human NK cells mediates antigen-specific immune responses
    Sci. Immunol (IF 13.44) Pub Date : 2020-10-16
    Victoria Stary, Ram Vinay Pandey, Johanna Strobl, Lisa Kleissl, Patrick Starlinger, David Pereyra, Wolfgang Weninger, Gottfried F. Fischer, Christoph Bock, Matthias Farlik, Georg Stary

    Adaptive features of natural killer (NK) cells have been reported in various species with different underlying mechanisms. It is unclear, however, which NK cell populations are capable of mounting antigen-specific recall responses and how such functions are regulated at the molecular level. Here, we identify and characterize a discrete population of CD49a+CD16− NK cells in the human liver that displays

    更新日期:2020-10-17
  • Unresponsiveness to inhaled antigen is governed by conventional dendritic cells and overridden during infection by monocytes
    Sci. Immunol (IF 13.44) Pub Date : 2020-10-09
    James G. Bedford, Melanie Heinlein, Alexandra L. Garnham, Thi H. O. Nguyen, Tom Loudovaris, Chenghao Ge, Stuart I. Mannering, Michael Elliott, Stuart G. Tangye, Katherine Kedzierska, Daniel H. D. Gray, William R. Heath, Linda M. Wakim

    The nasal-associated lymphoid tissues (NALTs) are mucosal-associated lymphoid organs embedded in the submucosa of the nasal passage. NALTs represent a known site for the deposition of inhaled antigens, but little is known of the mechanisms involved in the induction of immunity within this lymphoid tissue. We find that during the steady state, conventional dendritic cells (cDCs) within the NALTs suppress

    更新日期:2020-10-11
  • Persistence and decay of human antibody responses to the receptor binding domain of SARS-CoV-2 spike protein in COVID-19 patients
    Sci. Immunol (IF 13.44) Pub Date : 2020-10-08
    Anita S. Iyer, Forrest K. Jones, Ariana Nodoushani, Meagan Kelly, Margaret Becker, Damien Slater, Rachel Mills, Erica Teng, Mohammad Kamruzzaman, Wilfredo F. Garcia-Beltran, Michael Astudillo, Diane Yang, Tyler E. Miller, Elizabeth Oliver, Stephanie Fischinger, Caroline Atyeo, A. John Iafrate, Stephen B. Calderwood, Stephen A. Lauer, Jingyou Yu, Zhenfeng Li, Jared Feldman, Blake M. Hauser, Timothy

    We measured plasma and/or serum antibody responses to the receptor-binding domain (RBD) of the spike (S) protein of SARS-CoV-2 in 343 North American patients infected with SARS-CoV-2 (of which 93% required hospitalization) up to 122 days after symptom onset and compared them to responses in 1548 individuals whose blood samples were obtained prior to the pandemic. After setting seropositivity thresholds

    更新日期:2020-10-08
  • Persistence of serum and saliva antibody responses to SARS-CoV-2 spike antigens in COVID-19 patients
    Sci. Immunol (IF 13.44) Pub Date : 2020-10-08
    Baweleta Isho, Kento T. Abe, Michelle Zuo, Alainna J. Jamal, Bhavisha Rathod, Jenny H. Wang, Zhijie Li, Gary Chao, Olga L. Rojas, Yeo Myong Bang, Annie Pu, Natasha Christie-Holmes, Christian Gervais, Derek Ceccarelli, Payman Samavarchi-Tehrani, Furkan Guvenc, Patrick Budylowski, Angel Li, Aimee Paterson, Feng Yun Yue, Lina M. Marin, Lauren Caldwell, Jeffrey L. Wrana, Karen Colwill, Frank Sicheri, Samira

    While the antibody response to SARS-CoV-2 has been extensively studied in blood, relatively little is known about the antibody response in saliva and its relationship to systemic antibody levels. Here, we profiled by enzyme-linked immunosorbent assays (ELISAs) IgG, IgA and IgM responses to the SARS-CoV-2 spike protein (full length trimer) and its receptor-binding domain (RBD) in serum and saliva of

    更新日期:2020-10-08
  • Regulatory T cell control of systemic immunity and immunotherapy response in liver metastasis
    Sci. Immunol (IF 13.44) Pub Date : 2020-10-02
    James C. Lee, Sadaf Mehdizadeh, Jennifer Smith, Arabella Young, Ilgiz A. Mufazalov, Cody T. Mowery, Adil Daud, Jeffrey A. Bluestone

    Patients with cancer with liver metastasis demonstrate significantly worse outcomes than those without liver metastasis when treated with anti–PD-1 immunotherapy. The mechanism of liver metastases–induced reduction in systemic antitumor immunity is unclear. Using a dual-tumor immunocompetent mouse model, we found that the immune response to tumor antigen presence within the liver led to the systemic

    更新日期:2020-10-04
  • IL-22–induced cell extrusion and IL-18–induced cell death prevent and cure rotavirus infection
    Sci. Immunol (IF 13.44) Pub Date : 2020-10-02
    Zhan Zhang, Jun Zou, Zhenda Shi, Benyue Zhang, Lucie Etienne-Mesmin, Yanling Wang, Xuyan Shi, Feng Shao, Benoit Chassaing, Andrew T. Gewirtz

    Bacterial flagellin can elicit production of TLR5-mediated IL-22 and NLRC4-mediated IL-18 cytokines that act in concert to cure and prevent rotavirus (RV) infection. This study investigated the mechanism by which these cytokines act to impede RV. Although IL-18 and IL-22 induce each other’s expression, we found that IL-18 and IL-22 both impeded RV independently of one another and did so by distinct

    更新日期:2020-10-04
  • Aging Tregs need DCAFinating
    Sci. Immunol (IF 13.44) Pub Date : 2020-10-02
    Dachuan Dong, Jonathan S. Maltzman

    Loss of DCAF1 and resulting ROS leads to Treg aging and inflammation.

    更新日期:2020-10-04
  • MAIT cell activation and dynamics associated with COVID-19 disease severity
    Sci. Immunol (IF 13.44) Pub Date : 2020-09-28
    Tiphaine Parrot, Jean-Baptiste Gorin, Andrea Ponzetta, Kimia T. Maleki, Tobias Kammann, Johanna Emgård, André Perez-Potti, Takuya Sekine, Olga Rivera-Ballesteros, the Karolinska COVID-19 Study Group†, Sara Gredmark-Russ, Olav Rooyackers, Elin Folkesson, Lars I. Eriksson, Anna Norrby-Teglund, Hans-Gustaf Ljunggren, Niklas K. Björkström, Soo Aleman, Marcus Buggert, Jonas Klingström, Kristoffer Strålin

    Severe COVID-19 is characterized by excessive inflammation of the lower airways. The balance of protective versus pathological immune responses in COVID-19 is incompletely understood. Mucosa-associated invariant T (MAIT) cells are antimicrobial T cells that recognize bacterial metabolites, and can also function as innate-like sensors and mediators of antiviral responses. Here, we investigated the MAIT

    更新日期:2020-09-28
  • The myeloid type I interferon response to myocardial infarction begins in bone marrow and is regulated by Nrf2-activated macrophages
    Sci. Immunol (IF 13.44) Pub Date : 2020-09-25
    David M. Calcagno, Richard P. Ng, Avinash Toomu, Claire Zhang, Kenneth Huang, Aaron D. Aguirre, Ralph Weissleder, Lori B. Daniels, Zhenxing Fu, Kevin R. King

    Sterile tissue injury is thought to locally activate innate immune responses via damage-associated molecular patterns (DAMPs). Whether innate immune pathways are remotely activated remains relatively unexplored. Here, by analyzing ~145,000 single-cell transcriptomes at steady state and after myocardial infarction (MI) in mice and humans, we show that the type I interferon (IFN) response, characterized

    更新日期:2020-09-25
  • IL-21 from high-affinity CD4 T cells drives differentiation of brain-resident CD8 T cells during persistent viral infection.
    Sci. Immunol (IF 13.44) Pub Date : 2020-09-18
    Heather M Ren,Elizabeth M Kolawole,Mingqiang Ren,Ge Jin,Colleen S Netherby-Winslow,Quinn Wade,Shwetank,Ziaur S M Rahman,Brian D Evavold,Aron E Lukacher

    Development of tissue-resident memory (TRM) CD8 T cells depends on CD4 T cells. In polyomavirus central nervous system infection, brain CXCR5hi PD-1hi CD4 T cells produce interleukin-21 (IL-21), and CD8 T cells lacking IL-21 receptors (IL21R−/−) fail to become bTRM. IL-21+ CD4 T cells exhibit elevated T cell receptor (TCR) affinity and higher TCR density. IL21R−/− brain CD8 T cells do not express CD103

    更新日期:2020-09-20
  • Transcriptomic and clonal characterization of T cells in the human central nervous system.
    Sci. Immunol (IF 13.44) Pub Date : 2020-09-18
    Jenna L Pappalardo,Le Zhang,Maggie K Pecsok,Kelly Perlman,Chrysoula Zografou,Khadir Raddassi,Ahmad Abulaban,Smita Krishnaswamy,Jack Antel,David van Dijk,David A Hafler

    T cells provide critical immune surveillance to the central nervous system (CNS), and the cerebrospinal fluid (CSF) is thought to be a main route for their entry. Further characterization of the state of T cells in the CSF in healthy individuals is important for understanding how T cells provide protective immune surveillance without damaging the delicate environment of the CNS and providing tissue-specific

    更新日期:2020-09-20
  • Longitudinal immune profiling reveals key myeloid signatures associated with COVID-19.
    Sci. Immunol (IF 13.44) Pub Date : 2020-09-17
    Elizabeth R Mann,Madhvi Menon,Sean Blandin Knight,Joanne E Konkel,Christopher Jagger,Tovah N Shaw,Siddharth Krishnan,Magnus Rattray,Andrew Ustianowski,Nawar Diar Bakerly,Paul Dark,Graham Lord,Angela Simpson,Timothy Felton,Ling-Pei Ho,,Marc Feldmann,,John R Grainger,Tracy Hussell

    COVID-19 pathogenesis is associated with an exaggerated immune response. However, the specific cellular mediators and inflammatory components driving diverse clinical disease outcomes remain poorly understood. We undertook longitudinal immune profiling on both whole blood and peripheral blood mononuclear cells (PBMCs) of hospitalized patients during the peak of the COVID-19 pandemic in the UK. Here

    更新日期:2020-09-18
  • 更新日期:2020-09-18
  • Type I interferon signaling in fibroblastic reticular cells prevents exhaustive activation of antiviral CD8+ T cells.
    Sci. Immunol (IF 13.44) Pub Date : 2020-09-11
    Christian Perez-Shibayama,Ulrika Islander,Mechthild Lütge,Hung-Wei Cheng,Lucas Onder,Sandra S Ring,Angelina De Martin,Mario Novkovic,Julia Colston,Cristina Gil-Cruz,Burkhard Ludewig

    Fibroblastic reticular cells (FRCs) are stromal cells that actively promote the induction of immune responses by coordinating the interaction of innate and adaptive immune cells. However, whether and to which extent immune cell activation is determined by lymph node FRC reprogramming during acute viral infection has remained unexplored. Here, we genetically ablated expression of the type I interferon-α

    更新日期:2020-09-12
  • Sympathetic nervous tone limits the development of myeloid-derived suppressor cells.
    Sci. Immunol (IF 13.44) Pub Date : 2020-09-11
    James T Nevin,Marmar Moussa,William L Corwin,Ion I Mandoiu,Pramod K Srivastava

    Sympathetic nerves that innervate lymphoid organs regulate immune development and function by releasing norepinephrine that is sensed by immune cells via their expression of adrenergic receptors. Here, we demonstrate that ablation of sympathetic nervous system (SNS) signaling suppresses tumor immunity, and we dissect the mechanism of such immune suppression. We report that disruption of the SNS in

    更新日期:2020-09-12
  • The transcription factor E2A activates multiple enhancers that drive Rag expression in developing T and B cells.
    Sci. Immunol (IF 13.44) Pub Date : 2020-09-04
    Kazuko Miyazaki,Hitomi Watanabe,Genki Yoshikawa,Kenian Chen,Reiko Hidaka,Yuki Aitani,Kai Osawa,Rie Takeda,Yotaro Ochi,Shizue Tani-Ichi,Takuya Uehata,Osamu Takeuchi,Koichi Ikuta,Seishi Ogawa,Gen Kondoh,Yin C Lin,Hiroyuki Ogata,Masaki Miyazaki

    Cell type–specific gene expression is driven by the interplay between lineage-specific transcription factors and cis-regulatory elements to which they bind. Adaptive immunity relies on RAG-mediated assembly of T cell receptor (TCR) and immunoglobulin (Ig) genes. Although Rag1 and Rag2 expression is largely restricted to adaptive lymphoid lineage cells, it remains unclear how Rag gene expression is

    更新日期:2020-09-05
  • Immune surveillance of the liver by T cells.
    Sci. Immunol (IF 13.44) Pub Date : 2020-09-04
    Xenia Ficht,Matteo Iannacone

    The liver is the target of several infectious, inflammatory, and neoplastic diseases, which affect hundreds of millions of people worldwide and cause an estimated death toll of more than 2 million people each year. Dysregulation of T cell responses has been implicated in the pathogenesis of these diseases; hence, it is critically important to understand the function and fate of T cells in the liver

    更新日期:2020-09-05
  • Keepin' it regulatory: Foxp3 gets a BAFfling SWItch.
    Sci. Immunol (IF 13.44) Pub Date : 2020-09-04
    Maxime J Kinet,Michael D Rosenblum

    A novel role for SWI/SNF complexes in tuning Foxp3 expression and activity in Tregs.

    更新日期:2020-09-05
  • Illuminating the core of adaptive immunity-how the regulatory genome controls Rag chromatin dynamics.
    Sci. Immunol (IF 13.44) Pub Date : 2020-09-04
    Xun Wang,Ellen V Rothenberg

    E2A specifies adaptive immunity by instructing large-scale topological changes for Rag gene super-enhancer formation (see the related Research Article by Miyazaki et al.).

    更新日期:2020-09-05
  • Activation of TRPA1 nociceptor promotes systemic adult mammalian skin regeneration.
    Sci. Immunol (IF 13.44) Pub Date : 2020-08-28
    Jenny J Wei,Hali S Kim,Casey A Spencer,Donna Brennan-Crispi,Ying Zheng,Nicolette M Johnson,Misha Rosenbach,Christopher Miller,Denis H Leung,George Cotsarelis,Thomas H Leung

    Adult mammalian wounds, with rare exception, heal with fibrotic scars that severely disrupt tissue architecture and function. Regenerative medicine seeks methods to avoid scar formation and restore the original tissue structures. We show in three adult mouse models that pharmacologic activation of the nociceptor TRPA1 on cutaneous sensory neurons reduces scar formation and can also promote tissue regeneration

    更新日期:2020-08-29
  • Heterogeneity and clonal relationships of adaptive immune cells in ulcerative colitis revealed by single-cell analyses.
    Sci. Immunol (IF 13.44) Pub Date : 2020-08-21
    Brigid S Boland,Zhaoren He,Matthew S Tsai,Jocelyn G Olvera,Kyla D Omilusik,Han G Duong,Eleanor S Kim,Abigail E Limary,Wenhao Jin,J Justin Milner,Bingfei Yu,Shefali A Patel,Tiani L Louis,Tiffani Tysl,Nadia S Kurd,Alexandra Bortnick,Lauren K Quezada,Jad N Kanbar,Ara Miralles,Danny Huylebroeck,Mark A Valasek,Parambir S Dulai,Siddharth Singh,Li-Fan Lu,Jack D Bui,Cornelis Murre,William J Sandborn,Ananda

    Inflammatory bowel disease (IBD) encompasses a spectrum of gastrointestinal disorders driven by dysregulated immune responses against gut microbiota. We integrated single-cell RNA and antigen receptor sequencing to elucidate key components, cellular states, and clonal relationships of the peripheral and gastrointestinal mucosal immune systems in health and ulcerative colitis (UC). UC was associated

    更新日期:2020-08-23
  • Targeting Piezo1 unleashes innate immunity against cancer and infectious disease.
    Sci. Immunol (IF 13.44) Pub Date : 2020-08-21
    Berk Aykut,Ruonan Chen,Jacqueline I Kim,Dongling Wu,Sorin A A Shadaloey,Raquel Abengozar,Pamela Preiss,Anjana Saxena,Smruti Pushalkar,Joshua Leinwand,Brian Diskin,Wei Wang,Gregor Werba,Matthew Berman,Steve Ki Buom Lee,Alireza Khodadadi-Jamayran,Deepak Saxena,William A Coetzee,George Miller

    Piezo1 is a mechanosensitive ion channel that has gained recognition for its role in regulating diverse physiological processes. However, the influence of Piezo1 in inflammatory disease, including infection and tumor immunity, is not well studied. We postulated that Piezo1 links physical forces to immune regulation in myeloid cells. We found signal transduction via Piezo1 in myeloid cells and established

    更新日期:2020-08-23
  • Natural killer cell immunotypes related to COVID-19 disease severity.
    Sci. Immunol (IF 13.44) Pub Date : 2020-08-21
    Christopher Maucourant,Iva Filipovic,Andrea Ponzetta,Soo Aleman,Martin Cornillet,Laura Hertwig,Benedikt Strunz,Antonio Lentini,Björn Reinius,Demi Brownlie,Angelica Cuapio,Eivind Heggernes Ask,Ryan M Hull,Alvaro Haroun-Izquierdo,Marie Schaffer,Jonas Klingström,Elin Folkesson,Marcus Buggert,Johan K Sandberg,Lars I Eriksson,Olav Rooyackers,Hans-Gustaf Ljunggren,Karl-Johan Malmberg,Jakob Michaëlsson,Nicole

    Understanding innate immune responses in COVID-19 is important to decipher mechanisms of host responses and interpret disease pathogenesis. Natural killer (NK) cells are innate effector lymphocytes that respond to acute viral infections but might also contribute to immunopathology. Using 28-color flow cytometry, we here reveal strong NK cell activation across distinct subsets in peripheral blood of

    更新日期:2020-08-23
  • HVEM signaling promotes protective antibody-dependent cellular cytotoxicity (ADCC) vaccine responses to herpes simplex viruses.
    Sci. Immunol (IF 13.44) Pub Date : 2020-08-14
    Clare Burn Aschner,Lip Nam Loh,Benjamin Galen,Isabel Delwel,Rohit K Jangra,Scott J Garforth,Kartik Chandran,Steven Almo,William R Jacobs,Carl F Ware,Betsy C Herold

    Herpes simplex virus (HSV) glycoprotein D (gD) not only is required for virus entry and cell-to-cell spread but also binds the host immunomodulatory molecule, HVEM, blocking interactions with its ligands. Natural infection primarily elicits neutralizing antibodies targeting gD, but subunit protein vaccines designed to induce this response have failed clinically. In contrast, preclinical studies demonstrate

    更新日期:2020-08-14
  • An IL-2 mutein engineered to promote expansion of regulatory T cells arrests ongoing autoimmunity in mice.
    Sci. Immunol (IF 13.44) Pub Date : 2020-08-14
    Liliane Khoryati,Minh Nguyet Pham,McKenna Sherve,Swarnima Kumari,Kevin Cook,Josh Pearson,Marika Bogdani,Daniel J Campbell,Marc A Gavin

    Interleukin-2 (IL-2) controls the homeostasis and function of regulatory T (Treg) cells, and defects in the IL-2 pathway contribute to multiple autoimmune diseases. Although recombinant IL-2 therapy has been efficacious in certain inflammatory conditions, the capacity for IL-2 to also activate inflammatory effector responses highlights the need for IL-2–based therapeutics with improved Treg cell specificity

    更新日期:2020-08-14