Nature Immunology
@NatImmunol
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Nature Immunology is a multidisciplinary journal that publishes papers of the highest quality and significance in all areas of immunology.
New York, NY
Joined August 2015
The explosion of single-cell and systems approaches in immunology risks leaving the uninitiated behind. Bonaguro et al provide a guide to #Systems_immunology that is designed for immunologists who want an introduction to the area. DOI:10.1038/s41590-022-01309-9
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Neutrophils guide pre-existing matrix into injured organs to initiate tissue repair. News and Views by Ng.
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Epithelial cells use an immune-like mechanism to extrude and kill neighboring precancerous cells. Maruyama and colleagues demonstrate that LILRB3 on normal epithelial cells recognizes elevated Class I on transformed cells and triggers the extrusion process.
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In this resource Streets and colleagues provide a timeline of CD4+ and CD8+ T cell lineage commitment, identifying sequential waves of TCR signaling that initiate CD4+ T cell then CD8+ T cells lineage differentiation. Read it here:
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A multiomic atlas of T cell exhaustion in chronic viral infection reveals molecular programs of exhausted T cell subsets, divergent clonal exhausted T cell differentiation trajectories and suggests TCR signal strength as a driver of clonal fate
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Haas and colleagues use single cell multi-omics of human blood and bone marrow to generate a reference map allowing the quantitative linking of cytometry and proteo-genomic information.
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SARS-CoV-2 infection is milder in children. Dowell et al. show that immune responses are higher in children, retained for 12 months or longer and can neutralize Alpha, Beta and Delta variants. & see the Research Briefing
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Helper T cell subsets are characterized functionally by the cytokines they produce. Benoist and colleagues demonstrate that in vivo helper T cells do not manifest as discrete helper subsets but rather form a continuum shaped by microbial exposure
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Dubrot et al use genome-scale in vivo CRISPR screens to look at #immune_evasion mechanisms across #cancer models, showing that IFN-mediated upregulation of classical and non-classical MHC class I inhibitory checkpoints facilitate immune escape.
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Casali and colleagues describe a mouse model with a human lymphoid and myeloid immune system, that expresses BCR and TCR repertories as diverse as humans and mounts antibody responses to infection and vaccination. Read it here:
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Blacher et al find aging disrupts the myeloid circadian clock and identify KLF4 as a critical oscillating transcription factor that regulates macrophage gene expression and phagocytosis. @EranBlacher @StanfordMed
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New review: The transcription factor TCF-1 has multiple roles during T cell development and in mature T cells. Gounari and Khazaie review the potential mechanisms by which TCF-1 regulates gene expression
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Congratulations to Max Cooper and Jacques Miller for being awarded the Lasker award for the discovery of B and T cells!
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T cell exhaustion limits antitumor immune responses. Vignali and colleagues identify neuropilin-1 as a novel immune checkpoint that cell-intrinsically operates to limit memory cell formation and can be targeted to enhance antitumor responses.
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News and Views: LAG3 interferes with TCR signaling by lowering the pH in the vicinity of the TCR and inducing dissociation of the key signaling kinase Lck from the co-receptors CD8 and CD4
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The gut microbiota and their proximate immune cells engage in a dialog of reciprocal regulation. James and colleagues describe how immune cell and microbiotal populations vary along the length of the human colon.
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New resource paper by Albert and colleagues looking at variability of human immunity
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Congratulations to Jim Allison and Tasuku Honjo!!!.
BREAKING NEWS.The 2018 #NobelPrize in Physiology or Medicine has been awarded jointly to James P. Allison and Tasuku Honjo “for their discovery of cancer therapy by inhibition of negative immune regulation.”
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Philip and colleagues find that tumor-specific CD8+ T cells exhibit epigenetic modifications within hours of activation, before cell division. Continued antigen exposure drove further epigenetic remodeling. Read it here:
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The degree of plasticity in the epigenetic landscape of exhausted T cells has been unclear. Sen and colleagues find that exhausted CD8 T cells have a stable core epigenetic exhaustion signature that persists independent of inflammation or viral antigen.
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A time to be thankful. Although 2020 has been a difficult year, we thank the global #immunology community for the tremendous cooperation and collaboration to speed the development of vaccines against the SARS-CoV-2 virus and therapies for #COVID-19 patients.
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B cells regulate hematopoietic stem cells via cholinergic signaling. News and Views by Patel and Pietras
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The contribution of T cells to the SARS-CoV-2 response remains an important and unresolved question. Moss and colleagues examine T cell and antibody kinetics in a large cohort of patients with COVID-19 and find robust and durable T cell responses
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Christo etal find that the tissue in which tissue-resident memory T cells are generated dictates their properties and defines the TRM-cell-intrinsic sensitivity to signaling via the cytokine TGFβ. See also the N&V by McNamara & Cockburn. @LMackayLab
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Liston and colleagues design a gene-delivery system to specifically target astrocytes in the central nervous system to express IL-2 and thereby expand/maintain Treg cells to suppress neuroinflammation
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#Neutrophils can exhibit substantial function diversity. Montaldo et al @OstuniLab perform immunophenotyping and transcriptome analysis to characterize the heterogeneity of human neutrophils, both under steady state and upon stress-induced conditions.
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CD4+ T cells predominate the memory response in patients with COVID-19 severe disease, whereas higher proportions of CD8+ T cells were found in patients with mild disease.
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Arlene Sharpe and colleagues review salient aspects of CD8 T cell dysfunction, with a view of developing new ways to alleviate T cell exhaustion and enhance CD8 T cell functions in #cancer & #chronic_infection. @harvardmed 10.1038/s41590-021-00949-7
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New review: Smyth and colleagues provide an overview of recent advances in NK cell biology and discuss the progress and problems of NK cell–based cancer immunotherapies.
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Ma et al describe TetTCR-SeqHD - a method to simultaneously profile TCR sequences, cognate antigen specificities, targeted gene-expression, and surface-protein expression from tens of thousands of single cells.
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O’Sullivan and colleagues generate a comprehensive single-cell atlas of of human white adipose tissue to identify new cell states in health and obesity.
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How fibrosis and inflammation are integrated is not entirely clear. Susztak and colleagues show that profibrotic proximal tubular cells in the kidneys recruit basophils and activate them to produce interleukin-6 and drive TH17 cell responses
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Wang et al show that the mTORC2-Akt pathway is needed to maintain CD4⁺ memory cells. This axis suppresses mitoROS generation and subsequent oxidation of membrane phospholipids, preventing cell death by ferroptosis.
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#macrophages Chromatin undergoes extensive reprogramming during immune cell differentiation. Kuo and colleagues uncover an epigenetic mechanism that primes the chromatin to facilitate macrophage development
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Mucida and colleagues examine how the gut epithelial microenvironment alters CD4+ T cells during their conversion into intraepithelial lymphocytes. Chromatin accessibility and transcription changes triggered by ThPOK downregulation is required
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Joanna Groom points out in her Nature Immunology WorldView that it is time to rethink who and how we mentor. #Mentorship @WEHI_research @groomlab .
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How microglia sense amyloid plaques in AD is not clear. Lemke and colleagues report that TAM receptor kinases are required for normal microglial recognition of, response to and phagocytosis of Aβ plaques promoting the formation of dense-core plaques.
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Nahrendorf and colleagues show that B cells in the bone marrow are an important source of acetylcholine, which limits hematopoiesis through modulating the signals produced by the bone marrow stromal niche
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Sixt and colleagues show that different fibroblast populations in the lymph node mechanically control its swelling in a multitier fashion. See:
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FOXP3 deficiency dysregulates immune homeostasis. This multicenter collaboration finds FOXP3 deficiency only disrupts a few core genes, but this unmasks a degree of systemic inflammation, and it is this environment that then strongly perturbs Tregs
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@NatImmunol celebrates #WomensHistoryMonth by highlighting the contributions of women in immunology with specially commissioned content from women across the globe. #WomenInScience @4womeninscience .Check out our March issue .
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Brown and colleagues generated an atlas of miRNA expression profiles from mouse immune cells and connected these signatures with ATAC-seq, ChIP-seq and nascent RNA profiling. @Brown_lab1 .
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Luster and colleagues find that ST2+ Tregs can secrete IL-1Ra in response to IL-33 which reduces early IL-1-mediated innate immune responses during influenza infection. Read it here:
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Kedzierska and colleagues performed single-cell transcriptomic and paired TCRαβ analyses to map epitope-specific CD8+ T cell immunity across the human lifespan ex vivo in newborns, children, adults and older adults. Read it here:
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Bresser et al designed a reporter system to allow in vivo tracking of replicative history over many generations. They show stem-cell-like memory T cell pool that reconstitutes the CD8+ T cell effector pool upon reinfection is marked by prior quiescence
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Siliciano and colleagues describe the generation of bispecific antibodies that target HIV-1 and NK cells to enhance HIV-1-specific NK cell activity and reduce the viral reservoir. Read it here:
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July 2020 marks the 20th anniversary of Nature Immunology's launch. To celebrate, we have commissioned a series of Comments from some of our authors from the last 20 years describing their landmark studies and how they drove immunology research forward.
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The innate sensors of SARS-CoV-2 are still being determined. Kanneganti & colleagues find that the SARS-CoV-2 envelop protein is sensed by TLR2 and this drives pathogenic inflammatory cytokine production. #COVID19
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The British Society of Immunology has just launched a COVID vaccine hub. Stuffed with info. for the general public, educators, researchers and policy makers - check it out:
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Masopust and colleagues @Masopust_Vezys show that tissue-resident memory cells can reenter the circulation, and exhibit considerable plasticity, although they retain a proclivity to reestablish themselves in their tissue of origin.
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Tumor-associated macrophages (TAMs) support an immunosuppressive tumor microenvironment. Di Conza et al. uncover how ER stress responses pathways are engaged to orchestrate pro-tumorigenic features and survival in TAMs by tumor-derived lipids. @PCHo_Lab
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Vignali and colleagues report CD8+ T cells in the pancreatic islets have a LAG3-promoted ‘restrained’ phenotype resembling exhausted cells but maintain effector functions, and LAG3 expression limits pathology in the NOD mouse model of type 1 diabetes
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Good opportunity for students around the globe.
Together with my friend Carla Rothlin we are launching Global Immunotalks 2020 #globalimmuno.To be held Wednesdays 9 am PST starting 4/22 .ZOOM: Schedule at ..Hoping to benefit #immunology community globally Please pass the word!
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Glioblastoma is one of the most intractable tumors and presents a hypoxic and immunologically cold microenvironment. Lee and colleagues demonstrate that normalizing oxygen tension unleashes γδ T cell anti-glioblastoma function
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Wu et al report that T cells from patients with rheumatoid arthritis, mitochondrial aspartate is.deficient, resulting in ER expansion and excessive production of the pro-inflammatory cytokine.TNF. See also the N&V by Scherlinger & Tsokos
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Trispecific antibodies enhance the therapeutic efficacy of tumor-directed T cells| Lan Wu et al & Nabel lab | #Tumorimmunology #cancerimmunotherapy First publication in @NatureCancer N&V by Garfall & June @carlhjune
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Vivier and colleagues integrated scRNA-seq and CITE-seq data to provide a resource of human NK cell heterogeneity in healthy tissues and in the tumor setting. Read it here:
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Shlomchik and colleagues profile memory B cell subsets and their precursors to describe differences in genes and open chromatin regions. Read it here:
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Rudensky and colleagues find that Treg depletion in a PD-1 resistant cancer model vastly alters the TME and Treg dependent programs were identified, such as the VEGF pathway. Treg depletion and VEGF blockade improved tumor control
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Browse the Nature Collection on Stromal–Immune Cell interactions - now live at #Lymph_nodes #fibroblasts #mesenchymal_cells #inflammation #cancer.@NatImmunol @NatRevImmunol @Boehringer
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In their Perspective, Becher and colleagues propose an alternative framework in which to understand T helper diversity, based not on transcription factors and cytokines but rather physiological functionality. .@burkhard_becher
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Chen and colleagues define the stem-like program that controls the self-renewal capacity and effector differentiation potential of CD4+ effector precursor cells. Read it here:
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Minguet and colleagues find that CAR T cells containing CD3δ, CD3ε or CD3γ cytoplasmic tails are more effective than conventional ζ CAR T cells. Read it here:
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George Gao and colleagues designed a Zika virus vaccine that induces sterilizing immunity and fetal protection in mice challenged with ZIKV & that does not induce antibody-dependent enhancement on subsequent Dengue virus infection.
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Shlomchik and colleagues find that IL-12 initiates a B cell-intrinsic feed-forward loop between IL-12 and IFNγ which promotes B cell proliferation and plasmablast differentiation. Read it here:
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Perry et al. demonstrate that regulatory T (Treg) cell function is restrained by the cell-autonomous action of the checkpoint inhibitor molecule PD-1. This PD-1-dependent mechanism tunes Treg cell function during homeostasis and infection
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Andreakos discusses in @NatImmunol two new studies on how #SARS_CoV_2 infection triggers type I IFN-mediated immunopathology @VangelisAndrea1
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Chevrier and colleagues mapped the response to sepsis and describe a hierarchical cytokine module composed of TNF, IL-18, IFN-γ and IL-1β responsible for shaping the host response. Read it here:
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Klein and colleagues find that SARS-CoV-2 infection results in IL-1β-mediated hippocampal dysfunction leading to memory defects, which can be prevented by vaccination. Read it here:
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Thomas Korn and colleagues show skin and gut imprinted helper T cell subsets exhibit distinct function phenotypes in central nervous system autoimmunity. @TU_Muenchen
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New review: Godbout and colleagues discuss the neuroimmune mechanisms that underlie social-stress defeat, anxiety, and post-traumatic stress disorder
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Chi and colleagues identify brain-resident CXCR6+PD-1+CD8+ T cells that interact with microglia to limit immune-mediated pathology in a mouse model of Alzheimer’s disease. Read it here:
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Vignali and colleagues show that the inhibitory receptor LAG3 interferes with TCR signaling and T cell activation by lowering the pH at the immune synapse, which causes the dissociation of Lck from the CD4 or CD8 co-receptor
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New Resource! Sumida et al. resolve the human T cell transcriptional response to type IFN stimulation at high temporal resolution and reveal a genetic network controlling coinhibitory receptor expression
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Chronic viral infection leads to a dysregulation of germinal center B cell responses. Di Pietro et al show deletion of BMI-1 in mature B cells promotes effective humoral responses to chronic viral infection and accelerates viral clearance. @KimLJacobson
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SARS-CoV-2-specific CD4+ and CD8+ T cell epitopes are found in both convalescent patients and virus-naive volunteers and are indicative of heterologous recognition shared with seasonal cold viruses. @JulianeWalz
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Snell et al. examine the heterogeneity of CD4+ T cells in chronic viral infection, showing PD-L1 blockade enhances a cytotoxic gene program in antigen-specific TH1 cells. @brooks_lab @SnellLaura @pmcancercentre @uhn
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To determine how T cell lineage fates are determined in the thymus, Singer and colleagues generated ‘FlipFlop’ mice with a functionally reversed T cell immune system that distinguishes TCR signal strength versus TCR signal duration
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Sewell and colleagues show nonclassical MHC molecule MR1 is expressed on a wide variety of cancer types and can be targeted by conventional T cells.
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Sansom & colleagues highlight the pH-dependent differential manner in which CTLA-4 binds CD80 and CD86 in Treg cells and orchestrates immune tolerance regulation. .See also the N&V by Humphries & Lo.
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Liston et al review the diversity of the human immune system, which provides a potent defense against opportunistic pathogens. They discuss the key drivers and pathways in the causality of immune variation.
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Yu et al. review the roles played by follicular helper T cells in sustaining germinal center B cell responses and vaccination strategies, as well as potential pathogenic autoimmune responses. See
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Darcy, Beavis and colleagues use T cells engineered to express the dendritic cell growth factor Flt3L to co-opt the host endogenous adaptive immune response and control experimental tumor models. @unimelb @MacCullumCC @WEHI_research
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David Brooks and co. ( use mass cytometry to look at pre-existing T cell responses to type 1 interferon to predict patient survival and responsiveness to ICB therapy. For commentary see our News and Views:
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Calling attention to the upcoming #BlackInImmunoWeek November 22-28. See @BlackInImmuno for more information on the virtual events planned throughout the week.
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In these strange times- happy World Immunology Day everyone:.
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The transcription factor IRF8 is required for both DC and monocyte differentiation from common myeloid progenitors. Tamura and colleagues identify an enhancer (+56 kb) in the Irf8 locus that regulates early myeloid lineage choice
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Akassoglou and colleagues provide a resource of the responses of microglia and macrophages to blood proteins including activated complement and fibrin. Read it here:
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McGavern and colleagues find that monocytes produce IL-6 which instructs microglia to become repair associated microglia following intracerebral hemorrhage, which promotes neurological recovery. Read it here:
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Diversity matters. See the Comment by #AkikoIwasaki .@VirusesImmunity in the September issue of Nature Immunology. #DiversityAndInclusion
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Guo and colleagues describe a method for predicting and evaluating drugs to boost immune checkpoint blockade and find Taltirelin can improve anti-PD-1 efficacy by activating CD8+ T cells and DCs. Read it here:
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New review describing the multiple pathways to autoimmunity
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NK cells contribute to the destruction of tumors. Wei and colleagues demonstrate that NK cells within the tumor microenvironment undergo mitochondrial fragmentation leading to impairment of their function and survival.
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Sun and colleagues provide a new resource, multi-omics analysis of NK cell Jak–STAT signaling in response to the cytokines IL-2, IL-15, IL-12, IL-18 and IFN-α, showing synergistic and antagonistic interactions that govern NK cell activity.
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IL-2 is a classic T cell growth factor. Huang and colleagues demonstrate, however, that chronic IL-2 stimulation leads to a new exhaustion pathway that impairs antitumor immune responses.
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