4,791 results match your criteria Immunity[Journal]


Cytokine Networks in the Pathophysiology of Inflammatory Bowel Disease.

Immunity 2019 Apr;50(4):992-1006

Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Roosevelt Drive, Oxford OX3 7FY, UK; Translational Gastroenterology Unit, Experimental Medicine Division, Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK. Electronic address:

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract. Cytokine-targeted therapies have transformed the treatment of IBD, providing control of symptoms and longer relapse-free periods. However, many patients fail to respond, highlighting the need for therapies tailored to the underlying cell and molecular disease drivers. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.03.017DOI Listing
April 2019
20 Reads

The Cytokines of Asthma.

Immunity 2019 Apr;50(4):975-991

Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA; Cardiovascular Research Institute, University of California, San Francisco, San Francisco, USA.

Asthma is a chronic inflammatory airway disease associated with type 2 cytokines interleukin-4 (IL-4), IL-5, and IL-13, which promote airway eosinophilia, mucus overproduction, bronchial hyperresponsiveness (BHR), and immunogloubulin E (IgE) synthesis. However, only half of asthma patients exhibit signs of an exacerbated Type 2 response. "Type 2-low" asthma has different immune features: airway neutrophilia, obesity-related systemic inflammation, or in some cases, few signs of immune activation. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.03.018DOI Listing
April 2019
1 Read

Immune Signaling in Neurodegeneration.

Immunity 2019 Apr;50(4):955-974

Boston Children's Hospital, F.M. Kirby Neurobiology Center, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Howard Hughes Medical Institute, Boston Children's Hospital, Boston, MA, USA. Electronic address:

Neurodegenerative diseases of the central nervous system progressively rob patients of their memory, motor function, and ability to perform daily tasks. Advances in genetics and animal models are beginning to unearth an unexpected role of the immune system in disease onset and pathogenesis; however, the role of cytokines, growth factors, and other immune signaling pathways in disease pathogenesis is still being examined. Here we review recent genetic risk and genome-wide association studies and emerging mechanisms for three key immune pathways implicated in disease, the growth factor TGF-β, the complement cascade, and the extracellular receptor TREM2. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.03.016DOI Listing

Cytokine Circuits in Cardiovascular Disease.

Immunity 2019 Apr;50(4):941-954

Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63139, USA. Electronic address:

Arterial inflammation is a hallmark of atherosclerosis, and appropriate management of this inflammation represents a major unmet therapeutic need for cardiovascular disease patients. Here, we review the diverse contributions of immune cells to atherosclerosis, the mechanisms of immune cell activation in this context, and the cytokine circuits that underlie disease progression. We discuss the recent application of these insights in the form of immunotherapy to treat cardiovascular disease and highlight how studies on the cardiovascular co-morbidity that arises in autoimmunity might reveal additional roles for cytokines in atherosclerosis. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.03.007DOI Listing
April 2019
16 Reads

Transforming Growth Factor-β Signaling in Immunity and Cancer.

Immunity 2019 Apr;50(4):924-940

Cancer Biology and Genetics Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address:

Transforming growth factor (TGF)-β is a crucial enforcer of immune homeostasis and tolerance, inhibiting the expansion and function of many components of the immune system. Perturbations in TGF-β signaling underlie inflammatory diseases and promote tumor emergence. TGF-β is also central to immune suppression within the tumor microenvironment, and recent studies have revealed roles in tumor immune evasion and poor responses to cancer immunotherapy. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.03.024DOI Listing
April 2019
29 Reads

Shared and Distinct Functions of Type I and Type III Interferons.

Immunity 2019 Apr;50(4):907-923

Departments of Medicine, Pathology & Immunology, and Molecular Microbiology, and The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, Saint Louis, MO 63110, USA. Electronic address:

Type I interferons (IFNs) (IFN-α, IFN-β) and type III IFNs (IFN-λ) share many properties, including induction by viral infection, activation of shared signaling pathways, and transcriptional programs. However, recent discoveries have revealed context-specific functional differences. Here, we provide a comprehensive review of type I and type III IFN activities, highlighting shared and distinct features from molecular mechanisms through physiological responses. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.03.025DOI Listing
April 2019
22 Reads

The IL-17 Family of Cytokines in Health and Disease.

Immunity 2019 Apr;50(4):892-906

Division of Rheumatology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address:

The interleukin 17 (IL-17) family of cytokines contains 6 structurally related cytokines, IL-17A through IL-17F. IL-17A, the prototypical member of this family, just passed the 25 anniversary of its discovery. Although less is known about IL-17B-F, IL-17A (commonly known as IL-17) has received much attention for its pro-inflammatory role in autoimmune disease. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.03.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6474359PMC
April 2019
9 Reads

IL-10 Family Cytokines IL-10 and IL-22: from Basic Science to Clinical Translation.

Immunity 2019 Apr;50(4):871-891

Laboratory of Immunoregulation and Infection, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK. Electronic address:

Cytokines are among the most important effector and messenger molecules in the immune system. They profoundly participate in immune responses during infection and inflammation, protecting against or contributing to diseases such as allergy, autoimmunity, and cancer. Manipulating cytokine pathways, therefore, is one of the most effective strategies to treat various diseases. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.03.020DOI Listing
April 2019
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The Immunobiology of the Interleukin-12 Family: Room for Discovery.

Immunity 2019 Apr;50(4):851-870

Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, 4301 West Markham St., Little Rock, AR 72205, USA. Electronic address:

The discovery of interleukin (IL)-6 and its receptor subunits provided a foundation to understand the biology of a group of related cytokines: IL-12, IL-23, and IL-27. These family members utilize shared receptors and cytokine subunits and influence the outcome of cancer, infection, and inflammatory diseases. Consequently, many facets of their biology are being therapeutically targeted. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.03.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6472917PMC
April 2019
31 Reads

The γ Family of Cytokines: Basic Biology to Therapeutic Ramifications.

Immunity 2019 Apr;50(4):832-850

Molecular Immunology and Inflammation Branch, National Institute of Arthritis, Metabolic, and Skin Diseases, National Institutes of Health, Bethesda, MD 20892-1674, USA. Electronic address:

The common cytokine receptor γ chain, γ, is a component of the receptors for interleukin-2 (IL-2), IL-4, IL-7, IL-9, IL-15, and IL-21. Mutation of the gene encoding γ results in X-linked severe combined immunodeficiency in humans, and γ family cytokines collectively regulate development, proliferation, survival, and differentiation of immune cells. Here, we review the basic biology of these cytokines, highlighting mechanisms of signaling and gene regulation that have provided insights for immunodeficiency, autoimmunity, allergic diseases, and cancer. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.03.028DOI Listing
April 2019
10 Reads

Pleiotropy and Specificity: Insights from the Interleukin 6 Family of Cytokines.

Immunity 2019 Apr;50(4):812-831

Division of Molecular Psychoimmunology, Institute for Genetic Medicine and Graduate School of Medicine, Hokkaido University, Sapporo 060-0815, Japan; Headquarters, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan. Electronic address:

Since the molecular cloning of interleukin-6 (IL-6) in 1986, many other cytokines have been found to share the same signal transducer, gp130, in their receptor complexes. Thus, the IL-6 family of cytokines now consists of ten members. Although some of the family members' functions are redundant as a result of the expression of gp130, there are also functional distinctions between members. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.03.027DOI Listing
April 2019
1 Read

GM-CSF, IL-3, and IL-5 Family of Cytokines: Regulators of Inflammation.

Immunity 2019 Apr;50(4):796-811

Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Immunology, Harvard Medical School, Boston, MA, USA. Electronic address:

The β common chain cytokines GM-CSF, IL-3, and IL-5 regulate varied inflammatory responses that promote the rapid clearance of pathogens but also contribute to pathology in chronic inflammation. Therapeutic interventions manipulating these cytokines are approved for use in some cancers as well as allergic and autoimmune disease, and others show promising early clinical activity. These approaches are based on our understanding of the inflammatory roles of these cytokines; however, GM-CSF also participates in the resolution of inflammation, and IL-3 and IL-5 may also have such properties. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.03.022DOI Listing
April 2019
9 Reads

Interleukin-1 and Related Cytokines in the Regulation of Inflammation and Immunity.

Immunity 2019 Apr;50(4):778-795

IRCCS Humanitas Clinical and Research Center, via Manzoni 56, 20089 Rozzano Milan, Italy; Humanitas University, via Rita Levi Montalcini, 20090 Pieve Emanuele Milan, Italy. Electronic address:

Forty years after its naming, interleukin-1 (IL-1) is experiencing a renaissance brought on by the growing understanding of its context-dependent roles and advances in the clinic. Recent studies have identified important roles for members of the IL-1 family-IL-18, IL-33, IL-36, IL-37, and IL-38-in inflammation and immunity. Here, we review the complex functions of IL-1 family members in the orchestration of innate and adaptive immune responses and their diversity and plasticity. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.03.012DOI Listing

The Next Quarter Century.

Authors:

Immunity 2019 Apr;50(4):769-777

Immunity celebrates its 25th anniversary at an exciting time in immunology, marked by the advent of new, door-opening approaches and a deeper understanding of the centrality of the immune system to both health and disease. We asked 25 investigators to look forward and share a vision of the next quarter century of immunology research. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.03.029DOI Listing
April 2019
3 Reads

25 Years of Exciting Immunology.

Authors:

Immunity 2019 Apr;50(4):767-768

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http://dx.doi.org/10.1016/j.immuni.2019.03.030DOI Listing

Becalming Type 17 Inflammation in Ulcerative Colitis.

Immunity 2019 Apr;50(4):1029-1031

MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK; Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, UK. Electronic address:

Genome-wide association studies in ulcerative colitis point to a role for FcγRIIA, a receptor for IgG. Castro-Dopico et al. (2019) find a profound induction of anti-commensal IgG in the colonic mucosa of UC patients and outline a pathway whereby FcγR activation by IgG triggers IL-1β production, type 17 immunity, and the exacerbation of inflammation. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.03.019DOI Listing
April 2019
4 Reads

An X-ray Vision for Phosphoantigen Recognition.

Immunity 2019 Apr;50(4):1026-1028

CRCM, Immunity and Cancer Team, Institut Paoli-Calmettes, INSERM, CNRS, Aix Marseille Université, Marseille, France.

Invariant Vγ9Vδ2 T cells respond to "phosphoantigen" metabolites through binding to the B30.2 domain of butyrophilin BTN3A. Yang et al. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.03.015DOI Listing
April 2019
1 Read

Thrombin: A Gas Pedal Driving Innate Immunity.

Immunity 2019 Apr;50(4):1024-1026

Medizinische Klinik und Poliklinik I, Klinikum der Universität München, Munich, Germany; DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany. Electronic address:

Hemostasis and immunity were long considered entirely separate entities. In this issue of Immunity, Burzynski et al. (2019) find that thrombin, the key enzyme within the coagulation cascade, activates IL-1α, a central pleiotropic pro-inflammatory cytokine, to promote wound healing and platelet production following ectoderm injury. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.03.006DOI Listing
April 2019
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Targeting Interleukin-6 Signaling in Clinic.

Immunity 2019 Apr;50(4):1007-1023

Department of Immune Regulation, Immunology Frontier Research Center, Osaka University, 3-1 Yamadaoka, Suita City, Osaka, Japan. Electronic address:

Interleukin-6 (IL-6) is a pleiotropic cytokine with roles in immunity, tissue regeneration, and metabolism. Rapid production of IL-6 contributes to host defense during infection and tissue injury, but excessive synthesis of IL-6 and dysregulation of IL-6 receptor signaling is involved in disease pathology. Therapeutic agents targeting the IL-6 axis are effective in rheumatoid arthritis, and applications are being extended to other settings of acute and chronic inflammation. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.03.026DOI Listing
April 2019
20 Reads

Immunization with Components of the Viral Fusion Apparatus Elicits Antibodies That Neutralize Epstein-Barr Virus in B Cells and Epithelial Cells.

Immunity 2019 Apr 4. Epub 2019 Apr 4.

Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address:

Epstein-Barr virus (EBV) causes infectious mononucleosis and is associated with epithelial-cell cancers and B cell lymphomas. An effective EBV vaccine is not available. We found that antibodies to the EBV glycoprotein gH/gL complex were the principal components in human plasma that neutralized infection of epithelial cells and that antibodies to gH/gL and gp42 contributed to B cell neutralization. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.03.010DOI Listing
April 2019
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Single-Cell Transcriptomics of Human and Mouse Lung Cancers Reveals Conserved Myeloid Populations across Individuals and Species.

Immunity 2019 Apr 5. Epub 2019 Apr 5.

Department of Systems Biology, Harvard Medical School, Boston, MA, USA. Electronic address:

Tumor-infiltrating myeloid cells (TIMs) comprise monocytes, macrophages, dendritic cells, and neutrophils, and have emerged as key regulators of cancer growth. These cells can diversify into a spectrum of states, which might promote or limit tumor outgrowth but remain poorly understood. Here, we used single-cell RNA sequencing (scRNA-seq) to map TIMs in non-small-cell lung cancer patients. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.03.009DOI Listing
April 2019
1 Read

Loss of Neurological Disease HSAN-I-Associated Gene SPTLC2 Impairs CD8 T Cell Responses to Infection by Inhibiting T Cell Metabolic Fitness.

Immunity 2019 Mar 23. Epub 2019 Mar 23.

T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; Faculty of Biosciences, Heidelberg University, 69120 Heidelberg, Germany. Electronic address:

Patients with the neurological disorder HSAN-I suffer frequent infections, attributed to a lack of pain sensation and failure to seek care for minor injuries. Whether protective CD8 T cells are affected in HSAN-I patients remains unknown. Here, we report that HSAN-I-associated mutations in serine palmitoyltransferase subunit SPTLC2 dampened human T cell responses. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.03.005DOI Listing

Keratinocyte-Mediated Activation of the Cytokine TGF-β Maintains Skin Recirculating Memory CD8 T Cells.

Immunity 2019 Mar 23. Epub 2019 Mar 23.

Department of Dermatology, University of Pittsburgh, Pittsburgh, PA 15261, USA; Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15261, USA. Electronic address:

Regulated activation of the cytokine TGF-β by integrins αβ and αβ expressed on keratinocytes is required for residence of epidermal-resident memory T cells, but whether skin-derived signals also affect recirculating memory cells in the skin remains unclear. Here, we show that after resolution of skin vaccinia virus (VV) infection, antigen-specific circulating memory CD8 T cells migrated into skin. In mice lacking αβ and αβ integrins (Itgb6Itgb8-K14-cre), the absence of epidermal-activated TGF-β resulted in a gradual loss of E- or P-selectin-binding central and peripheral memory populations, which were rescued when skin entry was inhibited. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.03.002DOI Listing

An Id2-Reporter Mouse Redefines Innate Lymphoid Cell Precursor Potentials.

Immunity 2019 Apr 26;50(4):1054-1068.e3. Epub 2019 Mar 26.

Innate Immunity Unit, Institut Pasteur, Paris 75724, France; Inserm U1223, Institut Pasteur, Paris 75724, France. Electronic address:

Innate lymphoid cell (ILC) development proposes that ILC precursors (ILCPs) segregate along natural killer (NK) cell versus helper cell (ILC1, ILC2, ILC3) pathways, the latter depending on expression of Id2, Zbtb16, and Gata3. We have developed an Id2-reporter strain expressing red fluorescent protein (RFP) in the context of normal Id2 expression to re-examine ILCP phenotype and function. We show that bone-marrow ILCPs were heterogeneous and harbored extensive NK-cell potential in vivo and in vitro. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.02.022DOI Listing
April 2019
1 Read

Negative Co-stimulation Constrains T Cell Differentiation by Imposing Boundaries on Possible Cell States.

Immunity 2019 Apr 26;50(4):1084-1098.e10. Epub 2019 Mar 26.

Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Parker Institute for Cancer Immunotherapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address:

Co-stimulation regulates T cell activation, but it remains unclear whether co-stimulatory pathways also control T cell differentiation. We used mass cytometry to profile T cells generated in the genetic absence of the negative co-stimulatory molecules CTLA-4 and PD-1. Our data indicate that negative co-stimulation constrains the possible cell states that peripheral T cells can acquire. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.03.004DOI Listing
April 2019
21.561 Impact Factor

A Subset of Type I Conventional Dendritic Cells Controls Cutaneous Bacterial Infections through VEGFα-Mediated Recruitment of Neutrophils.

Immunity 2019 Apr 27;50(4):1069-1083.e8. Epub 2019 Mar 27.

Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), 8A Biomedical Grove, Biopolis, Singapore 138648, Singapore; Skin Research Institute of Singapore (SRIS), Agency for Science, Technology and Research (A(∗)STAR), 11 Mandalay Rd., Singapore 308232, Singapore. Electronic address:

Skin conventional dendritic cells (cDCs) exist as two distinct subsets, cDC1s and cDC2s, which maintain the balance of immunity to pathogens and tolerance to self and microbiota. Here, we examined the roles of dermal cDC1s and cDC2s during bacterial infection, notably Propionibacterium acnes (P. acnes). Read More

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http://dx.doi.org/10.1016/j.immuni.2019.03.001DOI Listing
April 2019
5 Reads

The Coagulation and Immune Systems Are Directly Linked through the Activation of Interleukin-1α by Thrombin.

Immunity 2019 Apr 26;50(4):1033-1042.e6. Epub 2019 Mar 26.

Division of Cardiovascular Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge, CB2 0QQ, UK. Electronic address:

Ancient organisms have a combined coagulation and immune system, and although links between inflammation and hemostasis exist in mammals, they are indirect and slower to act. Here we investigated direct links between mammalian immune and coagulation systems by examining cytokine proproteins for potential thrombin protease consensus sites. We found that interleukin (IL)-1α is directly activated by thrombin. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.03.003DOI Listing

A Weaning Reaction to Microbiota Is Required for Resistance to Immunopathologies in the Adult.

Immunity 2019 Mar 12. Epub 2019 Mar 12.

Microenvironment & Immunity Unit, Institut Pasteur, 75724 Paris, France; INSERM U1224, 75724 Paris, France. Electronic address:

Microbes colonize all body surfaces at birth and participate in the development of the immune system. In newborn mammals, the intestinal microbiota is first shaped by the dietary and immunological components of milk and then changes upon the introduction of solid food during weaning. Here, we explored the reactivity of the mouse intestinal immune system during the first weeks after birth and into adulthood. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.02.014DOI Listing
March 2019
10 Reads

A Structural Change in Butyrophilin upon Phosphoantigen Binding Underlies Phosphoantigen-Mediated Vγ9Vδ2 T Cell Activation.

Immunity 2019 Apr 19;50(4):1043-1053.e5. Epub 2019 Mar 19.

School of Pharmaceutical Sciences, Beijing Advanced Innovation Center for Structural Biology, MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Tsinghua University, Beijing 100084, China. Electronic address:

Human Vγ9Vδ2 T cells respond to microbial infections and malignancy by sensing diphosphate-containing metabolites called phosphoantigens, which bind to the intracellular domain of butyrophilin 3A1, triggering extracellular interactions with the Vγ9Vδ2 T cell receptor (TCR). Here, we examined the molecular basis of this "inside-out" triggering mechanism. Crystal structures of intracellular butyrophilin 3A proteins alone or in complex with the potent microbial phosphoantigen HMBPP or a synthetic analog revealed key features of phosphoantigens and butyrophilins required for γδ T cell activation. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.02.016DOI Listing
April 2019
8 Reads
21.561 Impact Factor

Treg-Cell Control of a CXCL5-IL-17 Inflammatory Axis Promotes Hair-Follicle-Stem-Cell Differentiation During Skin-Barrier Repair.

Immunity 2019 Mar;50(3):655-667.e4

Department of Dermatology, University of California, San Francisco, CA, USA. Electronic address:

Restoration of barrier-tissue integrity after injury is dependent on the function of immune cells and stem cells (SCs) residing in the tissue. In response to skin injury, hair-follicle stem cells (HFSCs), normally poised for hair generation, are recruited to the site of injury and differentiate into cells that repair damaged epithelium. We used a SC fate-mapping approach to examine the contribution of regulatory T (Treg) cells to epidermal-barrier repair after injury. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.02.013DOI Listing
March 2019
2 Reads

Viral DNA Binding to NLRC3, an Inhibitory Nucleic Acid Sensor, Unleashes STING, a Cyclic Dinucleotide Receptor that Activates Type I Interferon.

Immunity 2019 Mar;50(3):591-599.e6

Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address:

Immune suppression is a crucial component of immunoregulation and a subgroup of nucleotide-binding domain (NBD), leucine-rich repeat (LRR)-containing proteins (NLRs) attenuate innate immunity. How this inhibitory function is controlled is unknown. A key question is whether microbial ligands can regulate this inhibition. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.02.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6469509PMC
March 2019
10 Reads

Choreographing Immunity in the Skin Epithelial Barrier.

Immunity 2019 Mar;50(3):552-565

Cutaneous Leukocyte Biology Section, National Institutes of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA. Electronic address:

The skin interfaces with the external environment and is home to a myriad of immune cells that patrol the barrier to ward off harmful agents and aid in tissue repair. The formation of the cutaneous immune arsenal begins before birth and evolves throughout our lifetime, incorporating exogenous cues from microbes and inflammatory encounters, to achieve optimal fitness and function. Here, we discuss the context-specific signals that drive productive immune responses in the skin epithelium, highlighting key modulators of these reactions, including hair follicles, neurons, and commensal microbes. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.02.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6455972PMC
March 2019
1 Read

Recasting the Tissue-Resident Lymphocyte in Celiac Disease.

Immunity 2019 Mar;50(3):549-551

Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan; WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan. Electronic address:

In a recent issue of Cell, Mayassi et al. (2019) show that chronic inflammation in celiac disease (CeD) patients changes the repertoire and functional phenotype of intestinal TCR γδ intraepithelial lymphocytes. These changes are not reversed by gluten-free dietary regimens, suggesting that they might underlie the long-term sensitivity of CeD patients to gluten. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.02.020DOI Listing
March 2019
5 Reads

Exosomes Exercise Inhibition of Anti-Tumor Immunity during Chemotherapy.

Immunity 2019 Mar;50(3):547-549

Department of Cancer Biology, Metastasis Research Center, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA. Electronic address:

Exosomes are nano-sized extracellular vesicles that contain DNA, RNA, proteins, and lipids. Exosomes likely participate in facilitating intercellular communication and tumor growth. In this issue of Immunity, Zhang et al. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.02.019DOI Listing

Visualizing the Heterogeneity of Retinal Microglia.

Immunity 2019 Mar;50(3):544-546

Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis, MO, USA; Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA; Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO, USA. Electronic address:

In this issue of Immunity, O'Koren et al. (2019) report that murine retinal microglia are long lived and are divided into two spatially and functionally distinct niches in the retina. In models of retinal neurodegeneration, retinal microglia migrate to the subretinal space, an inducible disease-associated niche, where they are neuroprotective. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.02.017DOI Listing

Defining Barriers that Impede Choices.

Immunity 2019 Mar;50(3):542-544

Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA. Electronic address:

Committing to a differentiation pathway means leaving alternative pathways behind. Adoue et al. (2019) report that the H3K9-methyltrasferase Setdb1 plays a role in inhibiting the Th1 program in committed Th2 cells, and mechanistically, its role might relate to the selective targeting of endogenous retroviruses adjacent to Th1 enhancers. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S10747613193008
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http://dx.doi.org/10.1016/j.immuni.2019.02.021DOI Listing
March 2019
5 Reads

Sugar Fix Keeps RIPK3 at Bay.

Immunity 2019 Mar;50(3):539-541

Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, VIC 3168, Australia; Department of Molecular and Translational Science, Monash University, Clayton, VIC 3168, Australia. Electronic address:

Immunometabolism is emerging as an important modulator of immune responses. In this issue of Immunity, Li et al. (2019) examine the link between lipopolysaccharide (LPS)-induced glucose metabolism and innate immune signaling and identify how β-N-acetylglucosamine (O-GlcNAc) modification of the RIPK3 RHIM domain limits inflammation and necroptosis. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.02.018DOI Listing
March 2019
1 Read

The Miami Monkey: A Sunny Alternative to the Berlin Patient.

Immunity 2019 Mar;50(3):537-539

Aaron Diamond AIDS Research Center, The Rockefeller University, New York, NY, USA. Electronic address:

Curing HIV infection has been impossible, with the exception of the "Berlin Patient." Martinez-Navio et al. (2019) in Miami herein present a rare monkey whose virus was controlled for >3 years after a single genetic intervention that led to persistent production of HIV-neutralizing antibodies in vivo. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.02.010DOI Listing

Getting the Most from Your High-Dimensional Cytometry Data.

Immunity 2019 Mar;50(3):535-536

Institute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, Stanford, CA, USA. Electronic address:

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http://dx.doi.org/10.1016/j.immuni.2019.02.015DOI Listing

Anti-commensal IgG Drives Intestinal Inflammation and Type 17 Immunity in Ulcerative Colitis.

Immunity 2019 Apr 12;50(4):1099-1114.e10. Epub 2019 Mar 12.

Molecular Immunity Unit, University of Cambridge Department of Medicine, Cambridge CB2 0QH, UK; Cellular Genetics, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinton CB10 1SA, UK. Electronic address:

Inflammatory bowel disease is a chronic, relapsing condition with two subtypes, Crohn's disease (CD) and ulcerative colitis (UC). Genome-wide association studies (GWASs) in UC implicate a FCGR2A variant that alters the binding affinity of the antibody receptor it encodes, FcγRIIA, for immunoglobulin G (IgG). Here, we aimed to understand the mechanisms whereby changes in FcγRIIA affinity would affect inflammation in an IgA-dominated organ. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.02.006DOI Listing
April 2019
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Longitudinal Analysis Reveals Early Development of Three MPER-Directed Neutralizing Antibody Lineages from an HIV-1-Infected Individual.

Immunity 2019 Mar 12;50(3):677-691.e13. Epub 2019 Mar 12.

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. Electronic address:

Lineage-based vaccine design is an attractive approach for eliciting broadly neutralizing antibodies (bNAbs) against HIV-1. However, most bNAb lineages studied to date have features indicative of unusual recombination and/or development. From an individual in the prospective RV217 cohort, we identified three lineages of bNAbs targeting the membrane-proximal external region (MPER) of the HIV-1 envelope. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S10747613193007
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http://dx.doi.org/10.1016/j.immuni.2019.02.008DOI Listing
March 2019
3 Reads

Microglial Function Is Distinct in Different Anatomical Locations during Retinal Homeostasis and Degeneration.

Immunity 2019 Mar 5;50(3):723-737.e7. Epub 2019 Mar 5.

Department of Ophthalmology, Duke University, Durham, NC 27710, USA; Department of Immunology, Duke University, Durham, NC 27710, USA. Electronic address:

Microglia from different nervous system regions are molecularly and anatomically distinct, but whether they also have different functions is unknown. We combined lineage tracing, single-cell transcriptomics, and electrophysiology of the mouse retina and showed that adult retinal microglia shared a common developmental lineage and were long-lived but resided in two distinct niches. Microglia in these niches differed in their interleukin-34 dependency and functional contribution to visual-information processing. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.02.007DOI Listing
March 2019
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A Regulatory Circuit Controlling the Dynamics of NFκB cRel Transitions B Cells from Proliferation to Plasma Cell Differentiation.

Immunity 2019 Mar 5;50(3):616-628.e6. Epub 2019 Mar 5.

Signaling Systems Laboratory, Institute for Quantitative and Computational Biosciences and Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address:

Humoral immunity depends on efficient activation of B cells and their subsequent differentiation into antibody-secreting cells (ASCs). The transcription factor NFκB cRel is critical for B cell proliferation, but incorporating its known regulatory interactions into a mathematical model of the ASC differentiation circuit prevented ASC generation in simulations. Indeed, experimental ectopic cRel expression blocked ASC differentiation by inhibiting the transcription factor Blimp1, and in wild-type (WT) cells cRel was dynamically repressed during ASC differentiation by Blimp1 binding the Rel locus. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.02.004DOI Listing

Adeno-Associated Virus Delivery of Anti-HIV Monoclonal Antibodies Can Drive Long-Term Virologic Suppression.

Immunity 2019 Mar 5;50(3):567-575.e5. Epub 2019 Mar 5.

Department of Pathology, Miller School of Medicine, University of Miami, Miami, Florida, USA. Electronic address:

Long-term delivery of anti-HIV monoclonal antibodies (mAbs) using adeno-associated virus (AAV) vectors holds promise for the prevention and treatment of HIV infection. We describe a therapy trial in which four rhesus monkeys were infected with SHIV-AD8 for 86 weeks before receiving the AAV-encoded mAbs 3BNC117, 10-1074, and 10E8. Although anti-drug antibody (ADA) responses restricted mAb delivery, one monkey successfully maintained 50-150 μg/mL of 3BNC117 and 10-1074 for over 2 years. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.02.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457122PMC
March 2019
7 Reads

Dysregulated Lung Commensal Bacteria Drive Interleukin-17B Production to Promote Pulmonary Fibrosis through Their Outer Membrane Vesicles.

Immunity 2019 Mar 26;50(3):692-706.e7. Epub 2019 Feb 26.

CAS Key Laboratory of Tissue Microenvironment and Tumor, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 200031, China. Electronic address:

Idiopathic pulmonary fibrosis (IPF) is a severe form of lung fibrosis with a high mortality rate. However, the etiology of IPF remains unknown. Here, we report that alterations in lung microbiota critically promote pulmonary fibrosis pathogenesis. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.02.001DOI Listing
March 2019
3 Reads
21.561 Impact Factor

CCR7 Chemokine Receptor-Inducible lnc-Dpf3 Restrains Dendritic Cell Migration by Inhibiting HIF-1α-Mediated Glycolysis.

Immunity 2019 Mar 26;50(3):600-615.e15. Epub 2019 Feb 26.

National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai 200433, China; Department of Immunology & Center for Immunotherapy, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100005, China; Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China; College of Life Science, Nankai University, Tianjin 300071, China. Electronic address:

CCR7 chemokine receptor stimulation induces rapid but transient dendritic cell (DC) migration toward draining lymph nodes, which is critical for the initiation of protective immunity and maintenance of immune homeostasis. The mechanisms for terminating CCR7-mediated DC migration remain incompletely understood. Here we have identified a long non-coding RNA lnc-Dpf3 whose feedback restrained CCR7-mediated DC migration. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.01.021DOI Listing
March 2019
21.561 Impact Factor

Human Memory B Cells Harbor Diverse Cross-Neutralizing Antibodies against BK and JC Polyomaviruses.

Immunity 2019 Mar 26;50(3):668-676.e5. Epub 2019 Feb 26.

Novartis Institutes for BioMedical Research, Basel, Switzerland, Cambridge, MA, USA, and Emeryville, CA, USA. Electronic address:

Human polyomaviruses cause a common childhood infection worldwide and typically elicit a neutralizing antibody and cellular immune response, while establishing a dormant infection in the kidney with minimal clinical manifestations. However, viral reactivation can cause severe pathology in immunocompromised individuals. We developed a high-throughput, functional antibody screen to examine the humoral response to BK polyomavirus. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.02.003DOI Listing
March 2019
2 Reads