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  • Deciphering the ins and outs of SARS-CoV-2-specific T cells
    Nat. Immunol. (IF 20.479) Pub Date : 2020-11-26
    André Perez-Potti; Joshua Lange; Marcus Buggert

    Comprehensive analysis of specific and cross-reactive SARS-CoV-2 epitopes reveals functional T cell responses against specific viral regions in essentially all convalescent individuals and a majority of unexposed donors, demonstrating that cross-reactive responses to COVID-19 are widespread.

    更新日期:2020-11-27
  • Author Correction: The cellular composition of the human immune system is shaped by age and cohabitation
    Nat. Immunol. (IF 20.479) Pub Date : 2020-11-25
    Edward J. Carr; James Dooley; Josselyn E. Garcia-Perez; Vasiliki Lagou; James C. Lee; Carine Wouters; Isabelle Meyts; An Goris; Guy Boeckxstaens; Michelle A. Linterman; Adrian Liston

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

    更新日期:2020-11-25
  • Establishment of an African green monkey model for COVID-19 and protection against re-infection
    Nat. Immunol. (IF 20.479) Pub Date : 2020-11-24
    Courtney Woolsey; Viktoriya Borisevich; Abhishek N. Prasad; Krystle N. Agans; Daniel J. Deer; Natalie S. Dobias; John C. Heymann; Stephanie L. Foster; Corri B. Levine; Liana Medina; Kevin Melody; Joan B. Geisbert; Karla A. Fenton; Thomas W. Geisbert; Robert W. Cross

    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for an unprecedented global pandemic of COVID-19. Animal models are urgently needed to study the pathogenesis of COVID-19 and to screen vaccines and treatments. We show that African green monkeys (AGMs) support robust SARS-CoV-2 replication and develop pronounced respiratory disease, which may more accurately reflect human

    更新日期:2020-11-25
  • MEK inhibition reprograms CD8 + T lymphocytes into memory stem cells with potent antitumor effects
    Nat. Immunol. (IF 20.479) Pub Date : 2020-11-23
    Vivek Verma; Nazli Jafarzadeh; Shannon Boi; Subhadip Kundu; Zhinuo Jiang; Yiping Fan; Jose Lopez; Rahul Nandre; Peng Zeng; Fatmah Alolaqi; Shamim Ahmad; Pankaj Gaur; Simon T. Barry; Viia E. Valge-Archer; Paul D. Smith; Jacques Banchereau; Mikayel Mkrtichyan; Benjamin Youngblood; Paulo C. Rodriguez; Seema Gupta; Samir N. Khleif

    Regenerative stem cell–like memory (TSCM) CD8+ T cells persist longer and produce stronger effector functions. We found that MEK1/2 inhibition (MEKi) induces TSCM that have naive phenotype with self-renewability, enhanced multipotency and proliferative capacity. This is achieved by delaying cell division and enhancing mitochondrial biogenesis and fatty acid oxidation, without affecting T cell receptor-mediated

    更新日期:2020-11-23
  • Author Correction: Noncanonical binding of Lck to CD3ε promotes TCR signaling and CAR function
    Nat. Immunol. (IF 20.479) Pub Date : 2020-11-19
    Frederike A. Hartl; Esmeralda Beck-Garcìa; Nadine M. Woessner; Lea J. Flachsmann; Rubí M.-H. Velasco Cárdenas; Simon M. Brandl; Sanaz Taromi; Gina J. Fiala; Anna Morath; Pankaj Mishra; O. Sascha Yousefi; Julia Zimmermann; Nico Hoefflin; Maja Köhn; Birgitta M. Wöhrl; Robert Zeiser; Kristian Schweimer; Stefan Günther; Wolfgang W. Schamel; Susana Minguet

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

    更新日期:2020-11-19
  • Author Correction: A regulatory T cell Notch4–GDF15 axis licenses tissue inflammation in asthma
    Nat. Immunol. (IF 20.479) Pub Date : 2020-11-19
    Hani Harb; Emmanuel Stephen-Victor; Elena Crestani; Mehdi Benamar; Amir Massoud; Ye Cui; Louis-Marie Charbonnier; Sena Arbag; Safa Baris; Amparito Cunnigham; Juan Manuel Leyva-Castillo; Raif S. Geha; Amirhosein J. Mousavi; Boris Guennewig; Klaus Schmitz-Abe; Constantinos Sioutas; Wanda Phipatanakul; Talal A. Chatila

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

    更新日期:2020-11-19
  • Macrophage expression and prognostic significance of the long pentraxin PTX3 in COVID-19
    Nat. Immunol. (IF 20.479) Pub Date : 2020-11-18
    Enrico Brunetta; Marco Folci; Barbara Bottazzi; Maria De Santis; Giuseppe Gritti; Alessandro Protti; Sarah N. Mapelli; Stefanos Bonovas; Daniele Piovani; Roberto Leone; Ilaria My; Veronica Zanon; Gianmarco Spata; Monica Bacci; Domenico Supino; Silvia Carnevale; Marina Sironi; Sadaf Davoudian; Clelia Peano; Francesco Landi; Fabiano Di Marco; Federico Raimondi; Andrea Gianatti; Claudio Angelini; Alessandro

    Long pentraxin 3 (PTX3) is an essential component of humoral innate immunity, involved in resistance to selected pathogens and in the regulation of inflammation1,2,3. The present study was designed to assess the presence and significance of PTX3 in Coronavirus Disease 2019 (COVID-19)4,5,6,7. RNA-sequencing analysis of peripheral blood mononuclear cells, single-cell bioinformatics analysis and immunohistochemistry

    更新日期:2020-11-18
  • Author Correction: XBP-1 and the unfolded protein response (UPR)
    Nat. Immunol. (IF 20.479) Pub Date : 2020-11-12
    Laurie H. Glimcher; Ann-Hwee Lee; Neal N. Iwakoshi

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

    更新日期:2020-11-12
  • Scientific divagations: from signaling and transcription to chromatin changes in T cells
    Nat. Immunol. (IF 20.479) Pub Date : 2020-11-10
    Anjana Rao

    Anjana Rao describes the team effort to define the changes in chromatin accessibility in naive T cells during TH1 and TH2 cell differentiation after stimulation with TCR ligands and the appropriate cytokines. Her lab showed that differentiated TH1 and TH2 cells, which produce the cytokines IFN-γ and IL-4, respectively, displayed distinct patterns of DNase I hypersensitivity, histone acetylation and

    更新日期:2020-11-12
  • CRELD1 controls T cell homeostasis
    Nat. Immunol. (IF 20.479) Pub Date : 2020-11-09
    Fotini Gounari

    The natural variability of CRELD1 expression identified in comprehensive data sets from healthy individuals helps predict and establish its role in regulating T cell homeostasis.

    更新日期:2020-11-09
  • CRELD1 modulates homeostasis of the immune system in mice and humans
    Nat. Immunol. (IF 20.479) Pub Date : 2020-11-09
    Lorenzo Bonaguro; Maren Köhne; Lisa Schmidleithner; Jonas Schulte-Schrepping; Stefanie Warnat-Herresthal; Arik Horne; Paul Kern; Patrick Günther; Rob ter Horst; Martin Jaeger; Souad Rahmouni; Michel Georges; Christine S. Falk; Yang Li; Elvira Mass; Marc Beyer; Leo A. B. Joosten; Mihai G. Netea; Thomas Ulas; Joachim L. Schultze; Anna C. Aschenbrenner

    CRELD1 is a pivotal factor for heart development, the function of which is unknown in adult life. We here provide evidence that CRELD1 is an important gatekeeper of immune system homeostasis. Exploiting expression variance in large human cohorts contrasting individuals with the lowest and highest CRELD1 expression levels revealed strong phenotypic, functional and transcriptional differences, including

    更新日期:2020-11-09
  • Proinflammatory IgG Fc structures in patients with severe COVID-19
    Nat. Immunol. (IF 20.479) Pub Date : 2020-11-09
    Saborni Chakraborty; Joseph Gonzalez; Karlie Edwards; Vamsee Mallajosyula; Anthony S. Buzzanco; Robert Sherwood; Cindy Buffone; Nimish Kathale; Susan Providenza; Markus M. Xie; Jason R. Andrews; Catherine A. Blish; Upinder Singh; Haley Dugan; Patrick C. Wilson; Tho D. Pham; Scott D. Boyd; Kari C. Nadeau; Benjamin A. Pinsky; Sheng Zhang; Matthew J. Memoli; Jeffery K. Taubenberger; Tasha Morales; Jeffrey

    Severe acute respiratory syndrome coronavirus 2 infections can cause coronavirus disease 2019 (COVID-19), which manifests with a range of severities from mild illness to life-threatening pneumonia and multi-organ failure. Severe COVID-19 is characterized by an inflammatory signature, including high levels of inflammatory cytokines, alveolar inflammatory infiltrates and vascular microthrombi. Here we

    更新日期:2020-11-09
  • Distinct antibody responses to SARS-CoV-2 in children and adults across the COVID-19 clinical spectrum
    Nat. Immunol. (IF 20.479) Pub Date : 2020-11-05
    Stuart P. Weisberg; Thomas J. Connors; Yun Zhu; Matthew R. Baldwin; Wen-Hsuan Lin; Sandeep Wontakal; Peter A. Szabo; Steven B. Wells; Pranay Dogra; Joshua Gray; Emma Idzikowski; Debora Stelitano; Francesca T. Bovier; Julia Davis-Porada; Rei Matsumoto; Maya Meimei Li Poon; Michael Chait; Cyrille Mathieu; Branka Horvat; Didier Decimo; Krystalyn E. Hudson; Flavia Dei Zotti; Zachary C. Bitan; Francesca

    Clinical manifestations of COVID-19 caused by the new coronavirus SARS-CoV-2 are associated with age1,2. Adults develop respiratory symptoms, which can progress to acute respiratory distress syndrome (ARDS) in the most severe form, while children are largely spared from respiratory illness but can develop a life-threatening multisystem inflammatory syndrome (MIS-C)3,4,5. Here, we show distinct antibody

    更新日期:2020-11-06
  • A new cell subtype that confers neuroprotection
    Nat. Immunol. (IF 20.479) Pub Date : 2020-11-02
    Rhonda Voskuhl

    A subset of neutrophils with an immature phenotype confers neuroprotection in traumatic optic nerve and spinal cord injury. This study identifies a new target population of cells for therapeutic strategies to induce neural regeneration during injury.

    更新日期:2020-11-02
  • Overlapping B cell pathways in severe COVID-19 and lupus
    Nat. Immunol. (IF 20.479) Pub Date : 2020-11-02
    A. Darise Farris; Joel M. Guthridge

    An exaggerated extrafollicular B cell response characteristic of active systemic lupus erythematosus also characterizes the B cell response to SARS-CoV-2 in those with severe COVID-19.

    更新日期:2020-11-02
  • Intravenous nanoparticle vaccination generates stem-like TCF1 + neoantigen-specific CD8 + T cells
    Nat. Immunol. (IF 20.479) Pub Date : 2020-11-02
    Faezzah Baharom; Ramiro A. Ramirez-Valdez; Kennedy K. S. Tobin; Hidehiro Yamane; Charles-Antoine Dutertre; Ahad Khalilnezhad; Glennys V. Reynoso; Vincent L. Coble; Geoffrey M. Lynn; Matthew P. Mulè; Andrew J. Martins; John P. Finnigan; Xiao Meng Zhang; Jessica A. Hamerman; Nina Bhardwaj; John S. Tsang; Heather D. Hickman; Florent Ginhoux; Andrew S. Ishizuka; Robert A. Seder

    Personalized cancer vaccines are a promising approach for inducing T cell immunity to tumor neoantigens. Using a self-assembling nanoparticle vaccine that links neoantigen peptides to a Toll-like receptor 7/8 agonist (SNP-7/8a), we show how the route and dose alter the magnitude and quality of neoantigen-specific CD8+ T cells. Intravenous vaccination (SNP-IV) induced a higher proportion of TCF1+PD-1+CD8+

    更新日期:2020-11-02
  • Author Correction: A dynamic CD2-rich compartment at the outer edge of the immunological synapse boosts and integrates signals
    Nat. Immunol. (IF 20.479) Pub Date : 2020-10-29
    Philippos Demetriou; Enas Abu-Shah; Salvatore Valvo; Sarah McCuaig; Viveka Mayya; Audun Kvalvaag; Thomas Starkey; Kseniya Korobchevskaya; Lennard Y. W. Lee; Matthias Friedrich; Elizabeth Mann; Mikhail A. Kutuzov; Matteo Morotti; Nina Wietek; Heather Rada; Shamsideen Yusuf; Jehan Afrose; Anastasios Siokis; Michael Meyer-Hermann; Ahmed Ashour Ahmed; David Depoil; Michael L. Dustin

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

    更新日期:2020-10-30
  • T cell economics: precursor cells predict inflation
    Nat. Immunol. (IF 20.479) Pub Date : 2020-10-29
    Matthew A. Huggins; Sara E. Hamilton

    The presence of central memory precursor cells during the acute response to cytomegalovirus infection is the best predictor of whether a T cell family will contribute to the inflationary memory pool.

    更新日期:2020-10-30
  • Two parallel worlds of memory T cells
    Nat. Immunol. (IF 20.479) Pub Date : 2020-10-28
    Talyn Chu; Jacqueline Berner; Dietmar Zehn

    In contrast with the classical dogma that the pathways generating either memory or ‘exhausted’ T cells are strictly segregated, data now identify a clonally distinct hybrid memory T cell subpopulation with an exhausted phenotype.

    更新日期:2020-10-29
  • Early emergence of T central memory precursors programs clonal dominance during chronic viral infection
    Nat. Immunol. (IF 20.479) Pub Date : 2020-10-26
    Simon Grassmann; Lorenz Mihatsch; Jonas Mir; Atefeh Kazeroonian; Roza Rahimi; Sophie Flommersfeld; Kilian Schober; Inge Hensel; Justin Leube; Ludwig O. Pachmayr; Lorenz Kretschmer; Qin Zhang; Adrien Jolly; M. Zeeshan Chaudhry; Matthias Schiemann; Luka Cicin-Sain; Thomas Höfer; Dirk H. Busch; Michael Flossdorf; Veit R. Buchholz

    Chronic cytomegalovirus (CMV) infection leads to long-term maintenance of extraordinarily large CMV-specific T cell populations. The magnitude of this so-called ‘memory inflation’ is thought to mainly depend on antigenic stimulation during the chronic phase of infection. However, by mapping the long-term development of CD8+ T cell families derived from single naive precursors, we find that fate decisions

    更新日期:2020-10-28
  • A new neutrophil subset promotes CNS neuron survival and axon regeneration
    Nat. Immunol. (IF 20.479) Pub Date : 2020-10-26
    Andrew R. Sas; Kevin S. Carbajal; Andrew D. Jerome; Rajasree Menon; Choya Yoon; Ashley L. Kalinski; Roman J. Giger; Benjamin M. Segal

    Transected axons typically fail to regenerate in the central nervous system (CNS), resulting in chronic neurological disability in individuals with traumatic brain or spinal cord injury, glaucoma and ischemia–reperfusion injury of the eye. Although neuroinflammation is often depicted as detrimental, there is growing evidence that alternatively activated, reparative leukocyte subsets and their products

    更新日期:2020-10-28
  • Neuroinflammation after surgery: from mechanisms to therapeutic targets
    Nat. Immunol. (IF 20.479) Pub Date : 2020-10-19
    Ting Yang; Ravikanth Velagapudi; Niccolò Terrando

    Injury is a key driver of inflammation, a critical yet necessary response involving several mediators that is aimed at restoring tissue homeostasis. Inflammation in the central nervous system can be triggered by a variety of stimuli, some intrinsic to the brain and others arising from peripheral signals. Fine-tuned regulation of this response is crucial in a system that is vulnerable due to, for example

    更新日期:2020-10-19
  • A new lymphoid-primed progenitor marked by Dach1 downregulation identified with single cell multi-omics
    Nat. Immunol. (IF 20.479) Pub Date : 2020-10-19
    Daniela Amann-Zalcenstein; Luyi Tian; Jaring Schreuder; Sara Tomei; Dawn S. Lin; Kirsten A. Fairfax; Jessica E. Bolden; Mark D. McKenzie; Andrew Jarratt; Adrienne Hilton; Jacob T. Jackson; Ladina Di Rago; Matthew P. McCormack; Carolyn A. de Graaf; Olivia Stonehouse; Samir Taoudi; Warren S. Alexander; Stephen L. Nutt; Matthew E. Ritchie; Ashley P. Ng; Shalin H. Naik

    A classical view of blood cell development is that multipotent hematopoietic stem and progenitor cells (HSPCs) become lineage-restricted at defined stages. Lin−c-Kit+Sca-1+Flt3+ cells, termed lymphoid-primed multipotent progenitors (LMPPs), have lost megakaryocyte and erythroid potential but are heterogeneous in their fate. Here, through single-cell RNA sequencing, we identify the expression of Dach1

    更新日期:2020-10-19
  • Two subsets of stem-like CD8 + memory T cell progenitors with distinct fate commitments in humans
    Nat. Immunol. (IF 20.479) Pub Date : 2020-10-12
    Giovanni Galletti; Gabriele De Simone; Emilia M. C. Mazza; Simone Puccio; Claudia Mezzanotte; Timothy M. Bi; Alexey N. Davydov; Maria Metsger; Eloise Scamardella; Giorgia Alvisi; Federica De Paoli; Veronica Zanon; Alice Scarpa; Barbara Camisa; Federico S. Colombo; Achille Anselmo; Clelia Peano; Sara Polletti; Domenico Mavilio; Luca Gattinoni; Shannon K. Boi; Benjamin A. Youngblood; Rhiannon E. Jones;

    T cell memory relies on the generation of antigen-specific progenitors with stem-like properties. However, the identity of these progenitors has remained unclear, precluding a full understanding of the differentiation trajectories that underpin the heterogeneity of antigen-experienced T cells. We used a systematic approach guided by single-cell RNA-sequencing data to map the organizational structure

    更新日期:2020-10-12
  • Environmental pollutants and the immune response
    Nat. Immunol. (IF 20.479) Pub Date : 2020-10-12
    Takafumi Suzuki; Takanori Hidaka; Yoshito Kumagai; Masayuki Yamamoto

    Environmental pollution is one of the most serious challenges to health in the modern world. Pollutants alter immune responses and can provoke immunotoxicity. In this Review, we summarize the major environmental pollutants that are attracting wide-ranging concern and the molecular basis underlying their effects on the immune system. Xenobiotic receptors, including the aryl hydrocarbon receptor (AHR)

    更新日期:2020-10-12
  • Transcriptome dynamics of CD4 + T cells during malaria maps gradual transit from effector to memory
    Nat. Immunol. (IF 20.479) Pub Date : 2020-10-12
    Megan S. F. Soon; Hyun Jae Lee; Jessica A. Engel; Jasmin Straube; Bryce S. Thomas; Clara P. S. Pernold; Lachlan S. Clarke; Pawat Laohamonthonkul; Rohit N. Haldar; Cameron G. Williams; Lianne I. M. Lansink; Marcela L. Moreira; Michael Bramhall; Lambros T. Koufariotis; Scott Wood; Xi Chen; Kylie R. James; Tapio Lönnberg; Steven W. Lane; Gabrielle T. Belz; Christian R. Engwerda; David S. Khoury; Miles

    The dynamics of CD4+ T cell memory development remain to be examined at genome scale. In malaria-endemic regions, antimalarial chemoprevention protects long after its cessation and associates with effects on CD4+ T cells. We applied single-cell RNA sequencing and computational modelling to track memory development during Plasmodium infection and treatment. In the absence of central memory precursors

    更新日期:2020-10-12
  • Extrafollicular B cell responses correlate with neutralizing antibodies and morbidity in COVID-19
    Nat. Immunol. (IF 20.479) Pub Date : 2020-10-07
    Matthew C. Woodruff; Richard P. Ramonell; Doan C. Nguyen; Kevin S. Cashman; Ankur Singh Saini; Natalie S. Haddad; Ariel M. Ley; Shuya Kyu; J. Christina Howell; Tugba Ozturk; Saeyun Lee; Naveenchandra Suryadevara; James Brett Case; Regina Bugrovsky; Weirong Chen; Jacob Estrada; Andrea Morrison-Porter; Andrew Derrico; Fabliha A. Anam; Monika Sharma; Henry M. Wu; Sang N. Le; Scott A. Jenks; Christopher

    A wide spectrum of clinical manifestations has become a hallmark of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) COVID-19 pandemic, although the immunological underpinnings of diverse disease outcomes remain to be defined. We performed detailed characterization of B cell responses through high-dimensional flow cytometry to reveal substantial heterogeneity in both effector and immature

    更新日期:2020-10-07
  • TREML4 receptor regulates inflammation and innate immune cell death during polymicrobial sepsis
    Nat. Immunol. (IF 20.479) Pub Date : 2020-10-05
    Christina Nedeva; Joseph Menassa; Mubing Duan; Chuanxin Liu; Marcel Doerflinger; Andrew J. Kueh; Marco J. Herold; Pamali Fonseka; Thanh Kha Phan; Pierre Faou; Harinda Rajapaksha; Weisan Chen; Mark D. Hulett; Hamsa Puthalakath

    Sepsis is a biphasic disease characterized by an acute inflammatory response, followed by a prolonged immunosuppressive phase. Therapies aimed at controlling inflammation help to reduce the time patients with sepsis spend in intensive care units, but they do not lead to a reduction in overall mortality. Recently, the focus has been on addressing the immunosuppressive phase, often caused by apoptosis

    更新日期:2020-10-05
  • Migration-induced cell shattering due to DOCK8 deficiency causes a type 2–biased helper T cell response
    Nat. Immunol. (IF 20.479) Pub Date : 2020-10-05
    Caitlin Schneider; Connie Shen; Angelica A. Gopal; Todd Douglas; Benjamin Forestell; Keith D. Kauffman; Dakota Rogers; Patricio Artusa; Qian Zhang; Huie Jing; Alexandra F. Freeman; Daniel L. Barber; Irah L. King; Maya Saleh; Paul W. Wiseman; Helen C. Su; Judith N. Mandl

    Mutations that impact immune cell migration and result in immune deficiency illustrate the importance of cell movement in host defense. In humans, loss-of-function mutations in DOCK8, a guanine exchange factor involved in hematopoietic cell migration, lead to immunodeficiency and, paradoxically, allergic disease. Here, we demonstrate that, like humans, Dock8−/− mice have a profound type 2 CD4+ helper

    更新日期:2020-10-05
  • Disturbed mitochondrial dynamics in CD8 + TILs reinforce T cell exhaustion
    Nat. Immunol. (IF 20.479) Pub Date : 2020-10-05
    Yi-Ru Yu; Hana Imrichova; Haiping Wang; Tung Chao; Zhengtao Xiao; Min Gao; Marcela Rincon-Restrepo; Fabien Franco; Raphael Genolet; Wan-Chen Cheng; Camilla Jandus; George Coukos; Yi-Fan Jiang; Jason W. Locasale; Alfred Zippelius; Pu-Ste Liu; Li Tang; Christoph Bock; Nicola Vannini; Ping-Chih Ho

    The metabolic challenges present in tumors attenuate the metabolic fitness and antitumor activity of tumor-infiltrating T lymphocytes (TILs). However, it remains unclear whether persistent metabolic insufficiency can imprint permanent T cell dysfunction. We found that TILs accumulated depolarized mitochondria as a result of decreased mitophagy activity and displayed functional, transcriptomic and epigenetic

    更新日期:2020-10-05
  • Endothelial cells instruct macrophages on how to Rspond to lung injury
    Nat. Immunol. (IF 20.479) Pub Date : 2020-10-02
    Thomas Marichal

    The lung endothelial cell–derived angiocrine Rspondin3 activates Wnt–β-catenin signaling in interstitial macrophages, leading to a metabolic–epigenetic reprogramming of interstitial macrophages that drives anti-inflammatory responses and attenuates endotoxin-induced lung injury.

    更新日期:2020-10-02
  • SARS-CoV-2-derived peptides define heterologous and COVID-19-induced T cell recognition
    Nat. Immunol. (IF 20.479) Pub Date : 2020-09-30
    Annika Nelde; Tatjana Bilich; Jonas S. Heitmann; Yacine Maringer; Helmut R. Salih; Malte Roerden; Maren Lübke; Jens Bauer; Jonas Rieth; Marcel Wacker; Andreas Peter; Sebastian Hörber; Bjoern Traenkle; Philipp D. Kaiser; Ulrich Rothbauer; Matthias Becker; Daniel Junker; Gérard Krause; Monika Strengert; Nicole Schneiderhan-Marra; Markus F. Templin; Thomas O. Joos; Daniel J. Kowalewski; Vlatka Stos-Zweifel;

    T cell immunity is central for the control of viral infections. To characterize T cell immunity, but also for the development of vaccines, identification of exact viral T cell epitopes is fundamental. Here we identify and characterize multiple dominant and subdominant SARS-CoV-2 HLA class I and HLA-DR peptides as potential T cell epitopes in COVID-19 convalescent and unexposed individuals. SARS-CoV-2-specific

    更新日期:2020-09-30
  • An old BATF’s new T-ricks
    Nat. Immunol. (IF 20.479) Pub Date : 2020-09-28
    Caleb A. Lareau; Ansuman T. Satpathy

    Two studies reveal a role for the transcriptional regulator BATF3 as a T cell–intrinsic factor mediating effective memory responses. This finding opens future avenues of investigation and opportunities to enhance cellular immunotherapy.

    更新日期:2020-09-28
  • Strength of tonic T cell receptor signaling instructs T follicular helper cell–fate decisions
    Nat. Immunol. (IF 20.479) Pub Date : 2020-09-28
    Juliet M. Bartleson; Ashley A. Viehmann Milam; David L. Donermeyer; Stephen Horvath; Yu Xia; Takeshi Egawa; Paul M. Allen

    T follicular helper (TFH) cells are critical in adaptive immune responses to pathogens and vaccines; however, what drives the initiation of their developmental program remains unclear. Studies suggest that a T cell antigen receptor (TCR)-dependent mechanism may be responsible for the earliest TFH cell–fate decision, but a critical aspect of the TCR has been overlooked: tonic TCR signaling. We hypothesized

    更新日期:2020-09-28
  • Functional CRISPR dissection of gene networks controlling human regulatory T cell identity
    Nat. Immunol. (IF 20.479) Pub Date : 2020-09-28
    Kathrin Schumann; Siddharth S. Raju; Michael Lauber; Saskia Kolb; Eric Shifrut; Jessica T. Cortez; Nikolaos Skartsis; Vinh Q. Nguyen; Jonathan M. Woo; Theodore L. Roth; Ruby Yu; Michelle L. T. Nguyen; Dimitre R. Simeonov; David N. Nguyen; Sasha Targ; Rachel E. Gate; Qizhi Tang; Jeffrey A. Bluestone; Matthew H. Spitzer; Chun Jimmie Ye; Alexander Marson

    Human regulatory T (Treg) cells are essential for immune homeostasis. The transcription factor FOXP3 maintains Treg cell identity, yet the complete set of key transcription factors that control Treg cell gene expression remains unknown. Here, we used pooled and arrayed Cas9 ribonucleoprotein screens to identify transcription factors that regulate critical proteins in primary human Treg cells under

    更新日期:2020-09-28
  • Interleukin-33 activates regulatory T cells to suppress innate γδ T cell responses in the lung
    Nat. Immunol. (IF 20.479) Pub Date : 2020-09-28
    Lucas D. Faustino; Jason W. Griffith; Rod A. Rahimi; Keshav Nepal; Daniel L. Hamilos; Josalyn L. Cho; Benjamin D. Medoff; James J. Moon; Dario A. A. Vignali; Andrew D. Luster

    Foxp3+ regulatory T (Treg) cells expressing the interleukin (IL)-33 receptor ST2 mediate tissue repair in response to IL-33. Whether Treg cells also respond to the alarmin IL-33 to regulate specific aspects of the immune response is not known. Here we describe an unexpected function of ST2+ Treg cells in suppressing the innate immune response in the lung to environmental allergens without altering

    更新日期:2020-09-28
  • BATF3 programs CD8 + T cell memory
    Nat. Immunol. (IF 20.479) Pub Date : 2020-09-28
    Marco A. Ataide; Karl Komander; Konrad Knöpper; Annika E. Peters; Hao Wu; Sarah Eickhoff; Tea Gogishvili; Justus Weber; Anika Grafen; Axel Kallies; Natalio Garbi; Hermann Einsele; Michael Hudecek; Georg Gasteiger; Michael Hölzel; Martin Vaeth; Wolfgang Kastenmüller

    Antiviral CD8+ T cell responses are characterized by an initial activation/priming of T lymphocytes followed by a massive proliferation, subset differentiation, population contraction and the development of a stable memory pool. The transcription factor BATF3 has been shown to play a central role in the development of conventional dendritic cells, which in turn are critical for optimal priming of CD8+

    更新日期:2020-09-28
  • PD-1 + T reg cells: a foe in cancer immunotherapy?
    Nat. Immunol. (IF 20.479) Pub Date : 2020-09-24
    Halil-Ibrahim Aksoylar; Vassiliki A. Boussiotis

    The mechanisms that drive responses to PD-1-blocking immunotherapy in some but not all patients have been puzzling. A new study suggests that the balance of PD-1 expression levels between CD8+ T cells and Treg cells might provide an answer.

    更新日期:2020-09-24
  • Wnt and Hippo pathways in regulatory T cells: a NOTCH above in asthma.
    Nat. Immunol. (IF 20.479) Pub Date : 2020-09-23
    Hamida Hammad,Bart N Lambrecht

    The activation of the Notch4–Wnt–GDF15 axis in induced regulatory T (Treg cells) dampens their immunoregulatory function and turns them into TH2 and TH17 cytokine producers, allowing them to maintain ongoing allergic asthma.

    更新日期:2020-09-23
  • Publisher Correction: Tet2 and Tet3 in B cells are required to repress CD86 and prevent autoimmunity.
    Nat. Immunol. (IF 20.479) Pub Date : 2020-09-21
    Shinya Tanaka,Wataru Ise,Takeshi Inoue,Ayako Ito,Chisato Ono,Yoshihito Shima,Shuhei Sakakibara,Manabu Nakayama,Kentaro Fujii,Ikuo Miura,Jafar Sharif,Haruhiko Koseki,Pandelakis A Koni,Indu Raman,Quan-Zhen Li,Masato Kubo,Katsunori Fujiki,Ryuichiro Nakato,Katsuhiko Shirahige,Hiromitsu Araki,Fumihito Miura,Takashi Ito,Eiryo Kawakami,Yoshihiro Baba,Tomohiro Kurosaki

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

    更新日期:2020-09-21
  • IL-17: good fear no tears.
    Nat. Immunol. (IF 20.479) Pub Date : 2020-09-21
    Rejane Rua,Nathalie Pujol

    Cytokines are well-known mediators of the immune response, but, recently, pleiotropic roles in the central nervous system have started to be uncovered. It is now shown that IL-17 directly modulates fear behavior in mice.

    更新日期:2020-09-21
  • Lung mesenchymal cells elicit lipid storage in neutrophils that fuel breast cancer lung metastasis.
    Nat. Immunol. (IF 20.479) Pub Date : 2020-09-21
    Peishan Li,Ming Lu,Jiayuan Shi,Zheng Gong,Li Hua,Qing Li,Bora Lim,Xiang H-F Zhang,Xiaowen Chen,Sheng Li,Leonard D Shultz,Guangwen Ren

    Acquisition of a lipid-laden phenotype by immune cells has been defined in infectious diseases and atherosclerosis but remains largely uncharacterized in cancer. Here, in breast cancer models, we found that neutrophils are induced to accumulate neutral lipids upon interaction with resident mesenchymal cells in the premetastatic lung. Lung mesenchymal cells elicit this process through repressing the

    更新日期:2020-09-21
  • Author Correction: Tumor cells suppress radiation-induced immunity by hijacking caspase 9 signaling.
    Nat. Immunol. (IF 20.479) Pub Date : 2020-09-16
    Chuanhui Han,Zhida Liu,Yunjia Zhang,Aijun Shen,Chunbo Dong,Anli Zhang,Casey Moore,Zhenhua Ren,Changzheng Lu,Xuezhi Cao,Chun-Li Zhang,Jian Qiao,Yang-Xin Fu

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

    更新日期:2020-09-16
  • Author Correction: STEEP mediates STING ER exit and activation of signaling.
    Nat. Immunol. (IF 20.479) Pub Date : 2020-09-14
    Bao-Cun Zhang,Ramya Nandakumar,Line S Reinert,Jinrong Huang,Anders Laustsen,Zong-Liang Gao,Cheng-Long Sun,Søren Beck Jensen,Anne Troldborg,Sonia Assil,Martin F Berthelsen,Carsten Scavenius,Yan Zhang,Samuel J Windross,David Olagnier,Thaneas Prabakaran,Chiranjeevi Bodda,Ryo Narita,Yujia Cai,Cong-Gang Zhang,Harald Stenmark,Christine M Doucet,Takeshi Noda,Zheng Guo,Raphaela Goldbach-Mansky,Rune Hartmann

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

    更新日期:2020-09-14
  • A regulatory T cell Notch4-GDF15 axis licenses tissue inflammation in asthma.
    Nat. Immunol. (IF 20.479) Pub Date : 2020-09-14
    Hani Harb,Emmanuel Stephen-Victor,Elena Crestani,Mehdi Benamar,Amir Massoud,Ye Cui,Louis-Marie Charbonnier,Sena Arbag,Safa Baris,Amparito Cunnigham,Juan Manuel Leyva-Castillo,Raif S Geha,Amirhosein J Mousavi,Boris Guennewig,Klaus Schmitz-Abe,Constantinos Sioutas,Wanda Phipatanakul,Talal A Chatila

    Elucidating the mechanisms that sustain asthmatic inflammation is critical for precision therapies. We found that interleukin-6- and STAT3 transcription factor-dependent upregulation of Notch4 receptor on lung tissue regulatory T (Treg) cells is necessary for allergens and particulate matter pollutants to promote airway inflammation. Notch4 subverted Treg cells into the type 2 and type 17 helper (TH2

    更新日期:2020-09-14
  • Meningeal γδ T cells regulate anxiety-like behavior via IL-17a signaling in neurons.
    Nat. Immunol. (IF 20.479) Pub Date : 2020-09-14
    Kalil Alves de Lima,Justin Rustenhoven,Sandro Da Mesquita,Morgan Wall,Andrea Francesca Salvador,Igor Smirnov,Guilherme Martelossi Cebinelli,Tornike Mamuladze,Wendy Baker,Zach Papadopoulos,Maria Beatriz Lopes,William Sam Cao,Xinmin Simon Xie,Jasmin Herz,Jonathan Kipnis

    Interleukin (IL)-17a has been highly conserved during evolution of the vertebrate immune system and widely studied in contexts of infection and autoimmunity. Studies suggest that IL-17a promotes behavioral changes in experimental models of autism and aggregation behavior in worms. Here, through a cellular and molecular characterization of meningeal γδ17 T cells, we defined the nearest central nervous

    更新日期:2020-09-14
  • A dynamic CD2-rich compartment at the outer edge of the immunological synapse boosts and integrates signals.
    Nat. Immunol. (IF 20.479) Pub Date : 2020-09-14
    Philippos Demetriou,Enas Abu-Shah,Salvatore Valvo,Sarah McCuaig,Viveka Mayya,Audun Kvalvaag,Thomas Starkey,Kseniya Korobchevskaya,Lennard Y W Lee,Matthias Friedrich,Elizabeth Mann,Mikhail A Kutuzov,Matteo Morotti,Nina Wietek,Heather Rada,Shamsideen Yusuf,Jehan Afrose,Anastasios Siokis,,Michael Meyer-Hermann,Ahmed Ashour Ahmed,David Depoil,Michael L Dustin

    The CD2–CD58 recognition system promotes adhesion and signaling and counters exhaustion in human T cells. We found that CD2 localized to the outer edge of the mature immunological synapse, with cellular or artificial APC, in a pattern we refer to as a ‘CD2 corolla’. The corolla captured engaged CD28, ICOS, CD226 and SLAM-F1 co-stimulators. The corolla amplified active phosphorylated Src-family kinases

    更新日期:2020-09-14
  • Publisher Correction: Captain GBP1: inflammasomes assemble, pyroptotic endgame.
    Nat. Immunol. (IF 20.479) Pub Date : 2020-09-10
    Shouya Feng,Si Ming Man

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

    更新日期:2020-09-10
  • T cells in COVID-19 - united in diversity.
    Nat. Immunol. (IF 20.479) Pub Date : 2020-09-07
    Leo Swadling,Mala K Maini

    Comprehensive mapping reveals that functional CD4+ and CD8+ T cells targeting multiple regions of SARS-CoV-2 are maintained in the resolution phase of both mild and severe COVID-19, and their magnitude correlates with the antibody response.

    更新日期:2020-09-08
  • Limited proliferation capacity of aortic intima resident macrophages requires monocyte recruitment for atherosclerotic plaque progression.
    Nat. Immunol. (IF 20.479) Pub Date : 2020-09-07
    Jesse W Williams,Konstantin Zaitsev,Ki-Wook Kim,Stoyan Ivanov,Brian T Saunders,Patricia R Schrank,Kyeongdae Kim,Andrew Elvington,Seung Hyeon Kim,Christopher G Tucker,Mary Wohltmann,Brian T Fife,Slava Epelman,Maxim N Artyomov,Kory J Lavine,Bernd H Zinselmeyer,Jae-Hoon Choi,Gwendalyn J Randolph

    Early atherosclerosis depends upon responses by immune cells resident in the intimal aortic wall. Specifically, the healthy intima is thought to be populated by vascular dendritic cells (DCs) that, during hypercholesterolemia, initiate atherosclerosis by being the first to accumulate cholesterol. Whether these cells remain key players in later stages of disease is unknown. Using murine lineage-tracing

    更新日期:2020-09-08
  • Noel R. Rose 1927-2020.
    Nat. Immunol. (IF 20.479) Pub Date : 2020-09-07
    David W Scott,Rachel R Caspi,Kamal D Moudgil

    更新日期:2020-09-07
  • Broad and strong memory CD4+ and CD8+ T cells induced by SARS-CoV-2 in UK convalescent individuals following COVID-19.
    Nat. Immunol. (IF 20.479) Pub Date : 2020-09-04
    Yanchun Peng,Alexander J Mentzer,Guihai Liu,Xuan Yao,Zixi Yin,Danning Dong,Wanwisa Dejnirattisai,Timothy Rostron,Piyada Supasa,Chang Liu,César López-Camacho,Jose Slon-Campos,Yuguang Zhao,David I Stuart,Guido C Paesen,Jonathan M Grimes,Alfred A Antson,Oliver W Bayfield,Dorothy E D P Hawkins,De-Sheng Ker,Beibei Wang,Lance Turtle,Krishanthi Subramaniam,Paul Thomson,Ping Zhang,Christina Dold,Jeremy Ratcliff

    The development of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines and therapeutics will depend on understanding viral immunity. We studied T cell memory in 42 patients following recovery from COVID-19 (28 with mild disease and 14 with severe disease) and 16 unexposed donors, using interferon-γ-based assays with peptides spanning SARS-CoV-2 except ORF1. The breadth and magnitude

    更新日期:2020-09-05
  • Author Correction: Requirement for the basic helix-loop-helix transcription factor Dec2 in initial TH2 lineage commitment.
    Nat. Immunol. (IF 20.479) Pub Date : 2020-09-03
    Xuexian O Yang,Pornpimon Angkasekwinai,Jinfang Zhu,Juan Peng,Zhiduo Liu,Roza Nurieva,Xikui Liu,Yeonseok Chung,Seon Hee Chang,Bing Sun,Chen Dong

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

    更新日期:2020-09-03
  • Publisher Correction: SARS-CoV-2 infection of human ACE2-transgenic mice causes severe lung inflammation and impaired function.
    Nat. Immunol. (IF 20.479) Pub Date : 2020-09-02
    Emma S Winkler,Adam L Bailey,Natasha M Kafai,Sharmila Nair,Broc T McCune,Jinsheng Yu,Julie M Fox,Rita E Chen,James T Earnest,Shamus P Keeler,Jon H Ritter,Liang-I Kang,Sarah Dort,Annette Robichaud,Richard Head,Michael J Holtzman,Michael S Diamond

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

    更新日期:2020-09-02
  • Circulating TFH cells as a marker for early therapeutic intervention in T1D.
    Nat. Immunol. (IF 20.479) Pub Date : 2020-09-01
    Estelle Bettelli,Daniel J Campbell

    Costimulatory blockade via the CTLA-4–Ig fusion protein abatacept is beneficial in patients with early-onset type 1 diabetes, but some individuals benefit more than others. A new study reports that the pretreatment abundance of T follicular helper (TFH) cells could predict clinical responses to abatacept.

    更新日期:2020-09-01
  • NR4As apply brakes on the B cell response.
    Nat. Immunol. (IF 20.479) Pub Date : 2020-08-31
    Louisa Hill,Tanja A Schwickert

    To trigger an adequate humoral immune response while ensuring self-tolerance, B cell activation is tightly controlled. A new study indicates that an NR4A-enforced built-in brake fine-tunes the early phase of transcriptional reprogramming induced by BCR stimulation.

    更新日期:2020-08-31
  • NR4A nuclear receptors restrain B cell responses to antigen when second signals are absent or limiting.
    Nat. Immunol. (IF 20.479) Pub Date : 2020-08-31
    Corey Tan,Ryosuke Hiwa,James L Mueller,Vivasvan Vykunta,Kenta Hibiya,Mark Noviski,John Huizar,Jeremy F Brooks,Jose Garcia,Cheryl Heyn,Zhongmei Li,Alexander Marson,Julie Zikherman

    Antigen stimulation (signal 1) triggers B cell proliferation and primes B cells to recruit, engage and respond to T cell help (signal 2). Failure to receive signal 2 within a defined time window results in B cell apoptosis, yet the mechanisms that enforce dependence on co-stimulation are incompletely understood. Nr4a1–3 encode a small family of orphan nuclear receptors that are rapidly induced by B

    更新日期:2020-08-31
  • Dynamic regulation of hypoxia-inducible factor-1α activity is essential for normal B cell development.
    Nat. Immunol. (IF 20.479) Pub Date : 2020-08-31
    Natalie Burrows,Rachael J M Bashford-Rogers,Vijesh J Bhute,Ana Peñalver,John R Ferdinand,Benjamin J Stewart,Joscelin E G Smith,Mukta Deobagkar-Lele,Girolamo Giudice,Thomas M Connor,Akimichi Inaba,Laura Bergamaschi,Sam Smith,Maxine G B Tran,Evangelia Petsalaki,Paul A Lyons,Marion Espeli,Brian J P Huntly,Kenneth G C Smith,Richard J Cornall,Menna R Clatworthy,Patrick H Maxwell

    B lymphocyte development and selection are central to adaptive immunity and self-tolerance. These processes require B cell receptor (BCR) signaling and occur in bone marrow, an environment with variable hypoxia, but whether hypoxia-inducible factor (HIF) is involved is unknown. We show that HIF activity is high in human and murine bone marrow pro-B and pre-B cells and decreases at the immature B cell

    更新日期:2020-08-31
  • The PD-1 expression balance between effector and regulatory T cells predicts the clinical efficacy of PD-1 blockade therapies.
    Nat. Immunol. (IF 20.479) Pub Date : 2020-08-31
    Shogo Kumagai,Yosuke Togashi,Takahiro Kamada,Eri Sugiyama,Hitomi Nishinakamura,Yoshiko Takeuchi,Kochin Vitaly,Kota Itahashi,Yuka Maeda,Shigeyuki Matsui,Takuma Shibahara,Yasuho Yamashita,Takuma Irie,Ayaka Tsuge,Shota Fukuoka,Akihito Kawazoe