4,669 results match your criteria Immunity[Journal]
Immunity 2018 Nov 27. Epub 2018 Nov 27.
Walter Brendel Centre of Experimental Medicine, University Hospital, Ludwig Maximilians University of Munich, BioMedical Centre, 82152 Planegg-Martinsried, Germany; DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany; Department of Pathology and Immunology, Centre Médical Universitaire, University of Geneva, Switzerland. Electronic address:
The number of leukocytes present in circulation varies throughout the day, reflecting bone marrow output and emigration from blood into tissues. Using an organism-wide circadian screening approach, we detected oscillations in pro-migratory factors that were distinct for specific vascular beds and individual leukocyte subsets. This rhythmic molecular signature governed time-of-day-dependent homing behavior of leukocyte subsets to specific organs. Read More
Immunity 2018 Nov 21. Epub 2018 Nov 21.
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:
Microglia, the resident immune cells of the brain, rapidly change states in response to their environment, but we lack molecular and functional signatures of different microglial populations. Here, we analyzed the RNA expression patterns of more than 76,000 individual microglia in mice during development, in old age, and after brain injury. Our analysis uncovered at least nine transcriptionally distinct microglial states, which expressed unique sets of genes and were localized in the brain using specific markers. Read More
Immunity 2018 Nov;49(5):801-818
Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK. Electronic address:
Helminths are extraordinarily successful parasites due to their ability to modulate the host immune response. They have evolved a spectrum of immunomodulatory molecules that are now beginning to be defined, heralding a molecular revolution in parasite immunology. These discoveries have the potential both to transform our understanding of parasite adaptation to the host and to develop possible therapies for immune-mediated disease. Read More
Immunity 2018 Nov;49(5):798-800
Queen Mary University of London, Charterhouse Square, London EC1M6BQ, UK. Electronic address:
In a recent study published in Science, Albrengues et al. (2018) unveil an intriguing mechanism whereby the release of neutrophil extra-cellular traps during chronic lung inflammation awakens dormant malignant cells and contributes to cancer progression. Read More
Immunity 2018 Nov;49(5):796-798
Department of Immunology, Duke University School of Medicine, Durham, NC 27705, USA; Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC 27705, USA. Electronic address:
Researchers have previously hypothesized autoimmune origins for narcolepsy on the basis of its strong genetic association with an MHC class II allele. In a recent issue of Nature, Latorre et al. (2018) discovered that narcolepsy patients had autoreactive T cells specific to the neuronal antigen hypocretin, providing more evidence of the potential immune origin of the disease. Read More
Immunity 2018 Nov;49(5):793-795
Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110, USA. Electronic address:
The diversity of natural killer cells between mouse and human is poorly understood. In this issue of Immunity, Crinier et al. (2018) utilize single-cell RNA-seq to profile splenic and blood NK cells from both organisms, uncovering both tissue- and species-specific transcriptomic signatures. Read More
Immunity 2018 Nov;49(5):791-793
Department of Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada. Electronic address:
A key issue in immuno-oncology is how to optimize and combine antibody therapies for improved efficacy. In this issue of Immunity, Buchan et al. (2018) reveal the importance of antibody Fc region, Fc receptor availability, and sequence of administration for optimal cancer therapy with antibodies targeting the co-stimulatory receptor 4-1BB. Read More
Immunity 2018 Nov;49(5):788-790
Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden; Novo Nordisk Foundation Center for Basic Metabolic Research, Section for Metabolic Receptology and Enteroendocrinology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address:
While the commensal microbiota is considered an important regulator of immunity and metabolism, the mechanisms controlling the interplay between diet, cytokine signaling, and the microbiota in atherosclerosis remains unknown. In this issue of Immunity, Fatkhullina et al. (2018) demonstrate that interlukin-23-22 axis regulates diet-induced atherosclerosis by repressing pro-atherogenic microbiota. Read More
Immunity 2018 Nov;49(5):786-788
Department of Immunobiology, The University of Arizona College of Medicine, Tucson, AZ 85724, USA; The BIO-5 Institute, The University of Arizona College of Medicine, Tucson, AZ 85724, USA; The Arizona Center on Aging, The University of Arizona College of Medicine, Tucson, AZ 85724, USA; The University of Arizona Cancer Center, The University of Arizona College of Medicine, Tucson, AZ 85724, USA. Electronic address:
How the T cell receptor (TCR)-CD3 complex activates T cells is debated. In this issue of Immunity, Brazin et al. (2018) propose that TCR engagement under force releases the CD3 signaling modules to disperse and adopt signaling active states. Read More
Immunity 2018 Nov;49(5):783-785
Toronto General Hospital Research Institute, University Health Network; Department of Laboratory Medicine and Pathobiology, University of Toronto; Department of Immunology, University of Toronto; Peter Munk Cardiac Centre; Ted Rogers Centre for Heart Research, Toronto, ON, Canada. Electronic address:
Successful organ transplantation requires an optimal innate immune response to avoid tissue injury. In this issue of Immunity, Braza et al. (2018) inhibit pro-inflammatory activation of infiltrating graft macrophages using nanotechnology tools to promote immune tolerance, leading to long-term transplant acceptance in mouse models. Read More
Immunity 2018 Nov 6. Epub 2018 Nov 6.
Centre for Microvascular Research, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK; Centre for Inflammation and Therapeutic Innovation, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK. Electronic address:
Neutrophils require directional cues to navigate through the complex structure of venular walls and into inflamed tissues. Here we applied confocal intravital microscopy to analyze neutrophil emigration in cytokine-stimulated mouse cremaster muscles. We identified differential and non-redundant roles for the chemokines CXCL1 and CXCL2, governed by their distinct cellular sources. Read More
Immunity 2018 Nov 9. Epub 2018 Nov 9.
Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University, Atlanta, GA, USA; Immunology and Molecular Pathogenesis Program, Emory University, Atlanta, GA, USA. Electronic address:
Nutritional supplementation with probiotics can prevent pathologic bone loss. Here we examined the impact of supplementation with Lactobacillus rhamnosus GG (LGG) on bone homeostasis in eugonadic young mice. Micro-computed tomography revealed that LGG increased trabecular bone volume in mice, which was due to increased bone formation. Read More
Immunity 2018 Nov 13;49(5):958-970.e7. Epub 2018 Nov 13.
Antibody and Vaccine Group, Centre for Cancer Immunology, University of Southampton Faculty of Medicine, Southampton SO16 6YD, UK. Electronic address:
The costimulatory receptor 4-1BB is expressed on activated immune cells, including activated T cells. Antibodies targeting 4-1BB enhance the proliferation and survival of antigen-stimulated T cells in vitro and promote CD8 T cell-dependent anti-tumor immunity in pre-clinical cancer models. We found that T regulatory (Treg) cells infiltrating human or murine tumors expressed high amounts of 4-1BB. Read More
Immunity 2018 Nov 13;49(5):929-942.e5. Epub 2018 Nov 13.
Global Health Institute, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Station 19, 1015 Lausanne, Switzerland. Electronic address:
Commensal microbes colonize the gut epithelia of virtually all animals and provide several benefits to their hosts. Changes in commensal populations can lead to dysbiosis, which is associated with numerous pathologies and decreased lifespan. Peptidoglycan recognition proteins (PGRPs) are important regulators of the commensal microbiota and intestinal homeostasis. Read More
Immunity 2018 Nov 13;49(5):915-928.e5. Epub 2018 Nov 13.
Department of Infectious Diseases and Immunology, College of Veterinary Medicine, University of Florida, Gainesville, FL 32608, USA. Electronic address:
Innate lymphoid cells (ILCs) are important for mucosal immunity. The intestine harbors all ILC subsets, but how these cells are balanced to achieve immune homeostasis and mount appropriate responses during infection remains elusive. Here, we show that aryl hydrocarbon receptor (Ahr) expression in the gut regulates ILC balance. Read More
Immunity 2018 Nov 13;49(5):886-898.e5. Epub 2018 Nov 13.
Lineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address:
Pathogenic Th17 (pTh17) cells drive inflammation and immune-pathology, but whether pTh17 cells are a Th17 cell subset whose generation is under specific molecular control remains unaddressed. We found that Ras p21 protein activator 3 (RASA3) was highly expressed by pTh17 cells relative to non-pTh17 cells and was required specifically for pTh17 generation in vitro and in vivo. Mice conditionally deficient for Rasa3 in T cells showed less pathology during experimental autoimmune encephalomyelitis. Read More
Immunity 2018 Nov 6;49(5):857-872.e5. Epub 2018 Nov 6.
Department of Pathology, University of Massachusetts Medical School, Worcester, MA, 02135, USA. Electronic address:
Lineage-committed αβ and γδ T cells are thought to originate from common intrathymic multipotent progenitors following instructive T cell receptor (TCR) signals. A subset of lymph node and mucosal Vγ2 γδ T cells is programmed intrathymically to produce IL-17 (Tγδ17 cells), however the role of the γδTCR in development of these cells remains controversial. Here we generated reporter mice for the Tγδ17 lineage-defining transcription factor SOX13 and identified fetal-origin, intrathymic Sox13 progenitors. Read More
Immunity 2018 Nov 6;49(5):819-828.e6. Epub 2018 Nov 6.
Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Transplant Immunology Unit, National Center of Microbiology, Instituto de Salud Carlos III, Madrid, Spain. Electronic address:
Inducing graft acceptance without chronic immunosuppression remains an elusive goal in organ transplantation. Using an experimental transplantation mouse model, we demonstrate that local macrophage activation through dectin-1 and toll-like receptor 4 (TLR4) drives trained immunity-associated cytokine production during allograft rejection. We conducted nanoimmunotherapeutic studies and found that a short-term mTOR-specific high-density lipoprotein (HDL) nanobiologic treatment (mTORi-HDL) averted macrophage aerobic glycolysis and the epigenetic modifications underlying inflammatory cytokine production. Read More
Immunity 2018 Nov 6;49(5):971-986.e5. Epub 2018 Nov 6.
Aix Marseille Univ, CNRS, INSERM, Centre d'Immunologie de Marseille-Luminy, Marseille, France; Immunology, Marseille Immunopole, Hôpital de la Timone, Assistance Publique des Hôpitaux de Marseille, France; Innate Pharma Research Laboratories, Innate Pharma, Marseille, France. Electronic address:
Natural killer (NK) cells are innate lymphoid cells (ILCs) involved in antimicrobial and antitumoral responses. Several NK cell subsets have been reported in humans and mice, but their heterogeneity across organs and species remains poorly characterized. We assessed the diversity of human and mouse NK cells by single-cell RNA sequencing on thousands of individual cells isolated from spleen and blood. Read More
Immunity 2018 Nov 6;49(5):899-914.e6. Epub 2018 Nov 6.
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, US. Electronic address:
Interleukin-2 (IL-2) and downstream transcription factor STAT5 are important for maintaining regulatory T (Treg) cell homeostasis and function. Treg cells can respond to low IL-2 levels, but the mechanisms of STAT5 activation during partial IL-2 deficiency remain uncertain. We identified the serine-threonine kinase Mst1 as a signal-dependent amplifier of IL-2-STAT5 activity in Treg cells. Read More
Immunity 2018 Nov 30;49(5):829-841.e6. Epub 2018 Oct 30.
Laboratory of Immunobiology and Department of Medical Oncology, Dana-Farber Cancer Institute, and Department of Medicine, Harvard Medical School, Boston, MA 02115, USA. Electronic address:
Initial molecular details of cellular activation following αβT cell antigen receptor (TCR) ligation by peptide-major histocompatibility complexes (pMHC) remain unexplored. We determined the nuclear magnetic resonance (NMR) structure of the TCRα subunit transmembrane (TM) domain revealing a bipartite helix whose segmentation fosters dynamic movement. Positively charged TM residues Arg251 and Lys256 project from opposite faces of the helix, with Lys256 controlling immersion depth. Read More
Immunity 2018 Nov 30;49(5):943-957.e9. Epub 2018 Oct 30.
Blood Cell Development and Function Program, Fox Chase Cancer Center, Philadelphia, PA, 19111, USA. Electronic address:
Although commensal flora is involved in the regulation of immunity, the interplay between cytokine signaling and microbiota in atherosclerosis remains unknown. We found that interleukin (IL)-23 and its downstream target IL-22 restricted atherosclerosis by repressing pro-atherogenic microbiota. Inactivation of IL-23-IL-22 signaling led to deterioration of the intestinal barrier, dysbiosis, and expansion of pathogenic bacteria with distinct biosynthetic and metabolic properties, causing systemic increase in pro-atherogenic metabolites such as lipopolysaccharide (LPS) and trimethylamine N-oxide (TMAO). Read More
Immunity 2018 Nov 23;49(5):873-885.e7. Epub 2018 Oct 23.
Department of Pediatrics, Division of Infectious Diseases and Immunology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Biomedical Sciences, Infectious and Immunologic Disease Research Center, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Biomedical Science, Research Division of Immunology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA. Electronic address:
Receptor interacting protein 2 (RIP2) plays a role in sensing intracellular pathogens, but its function in T cells is unclear. We show that RIP2 deficiency in CD4 T cells resulted in chronic and severe interleukin-17A-mediated inflammation during Chlamydia pneumoniae lung infection, increased T helper 17 (Th17) cell formation in lungs of infected mice, accelerated atherosclerosis, and more severe experimental autoimmune encephalomyelitis. While RIP2 deficiency resulted in reduced conventional Th17 cell differentiation, it led to significantly enhanced differentiation of pathogenic (p)Th17 cells, which was dependent on RORα transcription factor and interleukin-1 but independent of nucleotide oligomerization domain (NOD) 1 and 2. Read More
Immunity 2018 Nov 23;49(5):842-856.e7. Epub 2018 Oct 23.
Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, P.R. China; Program in Molecular and Cellular Biology, Zhejiang University School of Medicine, Hangzhou 310058, P.R. China. Electronic address:
Cholesterol metabolism has been linked to immune functions, but the mechanisms by which cholesterol biosynthetic signaling orchestrates inflammasome activation remain unclear. Here, we have shown that NLRP3 inflammasome activation is integrated with the maturation of cholesterol master transcription factor SREBP2. Importantly, SCAP-SREBP2 complex endoplasmic reticulum-to-Golgi translocation was required for optimal activation of the NLRP3 inflammasome both in vitro and in vivo. Read More
Immunity 2018 Oct;49(4):782
Immunity 2018 Oct;49(4):780-781
Immunity 2018 Oct;49(4):764-779.e9
Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA. Electronic address:
The major types of non-small-cell lung cancer (NSCLC)-squamous cell carcinoma and adenocarcinoma-have distinct immune microenvironments. We developed a genetic model of squamous NSCLC on the basis of overexpression of the transcription factor Sox2, which specifies lung basal cell fate, and loss of the tumor suppressor Lkb1 (SL mice). SL tumors recapitulated gene-expression and immune-infiltrate features of human squamous NSCLC; such features included enrichment of tumor-associated neutrophils (TANs) and decreased expression of NKX2-1, a transcriptional regulator that specifies alveolar cell fate. Read More
Immunity 2018 Oct;49(4):754-763.e4
Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Cancer Research Laboratory, University of California, Berkeley, Berkeley, CA 94720, USA; Immunotherapeutics and Vaccine Research Initiative, University of California, Berkeley, Berkeley, CA 94720, USA. Electronic address:
Detection of cytosolic DNA by the enzyme cGAS triggers the production of cGAMP, a second messenger that binds and activates the adaptor protein STING, which leads to interferon (IFN) production. Here, we found that in vivo natural killer (NK) cell killing of tumor cells, but not of normal cells, depends on STING expression in non-tumor cells. Experiments using transplantable tumor models in STING- and cGAS-deficient mice revealed that cGAS expression by tumor cells was critical for tumor rejection by NK cells. Read More
Immunity 2018 Oct;49(4):640-653.e5
Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China; 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; College of Life Science, Nankai University, Tianjin 300071, China. Electronic address:
Tissue-resident mast cells are associated with many inflammatory and physiological processes. Although mast cells arise from the yolk sac, the exact ontogeny of adult mast cells remains unclear. Here we have investigated the hematopoietic origin of mast cells using fate-mapping systems. Read More
Immunity 2018 Oct;49(4):615-626.e6
Sanford-Burnham-Prebys Medical Discovery Institute, Orlando, Florida, USA; Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary; MTA-DE "Lendulet" Immunogenomics Research Group, University of Debrecen, Debrecen, Hungary. Electronic address:
Macrophages polarize into distinct phenotypes in response to complex environmental cues. We found that the nuclear receptor PPARγ drove robust phenotypic changes in macrophages upon repeated stimulation with interleukin (IL)-4. The functions of PPARγ on macrophage polarization in this setting were independent of ligand binding. Read More
Immunity 2018 Oct;49(4):595-613
Division of Medicine, University College London, London, England, UK. Electronic address:
Novel experimental approaches such as fate-mapping and single-cell analysis have brought fresh insight into monocyte development and function over the past decade and helped redefine the monocyte field. Monocytes are now known to consist of multiple subsets generated through distinct developmental pathways with diverse functional specializations. Their fates under homeostatic conditions include the accumulation in peripheral reservoirs and the engraftment into certain resident macrophage pools. Read More
Immunity 2018 Oct;49(4):592-594
VIB-Center for Cancer Biology, Department of Oncology, Katholieke Universiteit Leuven, 3000 Leuven, Belgium; Brain Tumor Research Center, Department of Neurological Surgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address:
Glioblastoma are highly immunosuppressive brain tumors that are known for their T cell paucity. In a recent issue of Nature Medicine, Chongsathidkiet et al. (2018) discovered a brain-specific mechanism of tumors to escape immunosurveillance by trapping T cells in the bone marrow through the loss of sphingosine-1-phosphate (S1P) receptor on the T cell surface. Read More
Immunity 2018 Oct;49(4):590-592
Centre for Inflammation Research, University of Edinburgh, Edinburgh EH16 4TJ, UK. Electronic address:
In a recent issue of Nature, Ordovas-Montanes et al. (2018) used cutting-edge genomic, epigenetic, and interventional techniques to characterize the cellular ecosystem in allergic chronic rhinosinusitis. They showed that basal epithelial cells "remember" type 2 inflammatory stimuli to maintain a chronic allergic disease phenotype. Read More
Immunity 2018 Oct;49(4):587-589
Yale University School of Medicine, Department of Immunobiology, New Haven, CT 06519, USA. Electronic address:
The factors that shape the distinctive tumor-immune landscapes of various types and subtypes of cancer remain poorly understood. In this issue of Immunity, Mollaoglu et al. (2018) reveal a mechanistic link between the function of lineage specifiers SOX2 and NKX2-1 and the presence of neutrophils in the tumor-immune microenvironment of lung cancer. Read More
Immunity 2018 Oct;49(4):585-587
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA. Electronic address:
Type I interferon (IFN) production within the tumor microenvironment is important in shaping the immune response to the tumor. In this issue of Immunity, Marcus et al. (2018) reveal that tumor cells produce 2'3'-cGAMP, which activates the STING pathway in non-tumor cells and leads to type I IFN production and the priming of natural killer cells for tumor rejection. Read More
Immunity 2018 Oct;49(4):582-584
Graduate School of Medical Science & Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 34141, Korea. Electronic address:
Recognition of cytoplasmic lipopolysaccharide (LPS) by caspase-11 leads to pyroptosis and secretion of inflammatory mediators. In this issue of Immunity, Deng et al. (2018) report that high-mobility group box 1 (HMGB1) secreted by hepatocytes delivers extracellular LPS into the cytoplasm and mediates pyroptosis. Read More
Immunity 2018 Oct;49(4):579-582
Department of Immunobiology, School of Medicine, Yale University, New Haven, CT 06510, USA; Department of Pharmacology, School of Medicine, Yale University, New Haven, CT 06510, USA. Electronic address:
Resolution of the immune response requires a coordinated effort to dampen inflammatory mediators and remove dying cells and debris. In this issue of Immunity, Proto et al. (2018) describe a circuit by which regulatory T cells enhance macrophage consumption of apoptotic cells during resolution. Read More
Immunity 2018 Oct;49(4):577-579
Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla CA, USA. Electronic address:
In this issue of Immunity, Daniel et al. (2018a) demonstrate that the nuclear receptor PPARγ acts in a ligand-insensitive manner to impart transcriptional memory and enhanced functionality to IL-4 polarized macrophages. Their findings shed light on the mechanisms that control priming of the epigenome in response to inflammatory signals. Read More
Immunity 2018 Oct 9;49(4):740-753.e7. Epub 2018 Oct 9.
Department of Hematology and Key Laboratory of Non-resolving Inflammation and Cancer of Hunan Province, The 3rd Xiangya Hospital, Central South University, Changsha 410000, P.R. China; Key Laboratory of Medical Genetics, School of Biological Science and Technology, Central South University, Changsha, Hunan Province 410000, P.R. China; Key Laboratory of Sepsis Translational Medicine of Hunan, Central South University, Changsha, Hunan Province 410000, P.R. China. Electronic address:
Caspase-11, a cytosolic endotoxin (lipopolysaccharide: LPS) receptor, mediates pyroptosis, a lytic form of cell death. Caspase-11-dependent pyroptosis mediates lethality in endotoxemia, but it is unclear how LPS is delivered into the cytosol for the activation of caspase-11. Here we discovered that hepatocyte-released high mobility group box 1 (HMGB1) was required for caspase-11-dependent pyroptosis and lethality in endotoxemia and bacterial sepsis. Read More
Immunity 2018 Oct 9;49(4):725-739.e6. Epub 2018 Oct 9.
Department of Medicine, Division of Rheumatology, Lowance Center for Human Immunology, Emory University, Atlanta, GA, USA. Electronic address:
Systemic Lupus Erythematosus (SLE) is characterized by B cells lacking IgD and CD27 (double negative; DN). We show that DN cell expansions reflected a subset of CXCR5 CD11c cells (DN2) representing pre-plasma cells (PC). DN2 cells predominated in African-American patients with active disease and nephritis, anti-Smith and anti-RNA autoantibodies. Read More
Immunity 2018 Oct 9;49(4):678-694.e5. Epub 2018 Oct 9.
Princess Margaret Cancer Center, University Health Network, Toronto, ON, M5G 2M9 Canada; Department of Immunology, University of Toronto, Toronto, ON, M5S 1A8 Canada. Electronic address:
CD8 T cell exhaustion impedes control of chronic viral infection; yet how new T cell responses are mounted during chronic infection is unclear. Unlike T cells primed at the onset of infection that rapidly differentiate into effectors and exhaust, we demonstrate that virus-specific CD8 T cells primed after establishment of chronic LCMV infection preferentially generate memory-like transcription factor TCF1 cells that were transcriptionally and proteomically distinct, less exhausted, and more responsive to immunotherapy. Mechanistically, adaptations of antigen-presenting cells and diminished T cell signaling intensity promoted differentiation of the memory-like subset at the expense of rapid effector cell differentiation, which was now highly dependent on IL-21-mediated CD4 T cell help for its functional generation. Read More
Immunity 2018 Oct 9;49(4):627-639.e6. Epub 2018 Oct 9.
Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York, 10461, USA; Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, 10461, USA; The Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, Bronx, New York, 10461, USA. Electronic address:
The non-hematopoietic cell fraction of the bone marrow (BM) is classically identified as CD45 Ter119 CD31 (herein referred to as triple-negative cells or TNCs). Although TNCs are believed to contain heterogeneous stromal cell populations, they remain poorly defined. Here we showed that the vast majority of TNCs (∼85%) have a hematopoietic rather than mesenchymal origin. Read More
Immunity 2018 Oct 2;49(4):666-677.e6. Epub 2018 Oct 2.
Department of Medicine, Columbia University, New York, NY 10032, USA; Department of Physiology and Cellular Biophysics, Columbia University, New York, NY 10032, USA; Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA. Electronic address:
Regulatory T (Treg) cell responses and apoptotic cell clearance (efferocytosis) represent critical arms of the inflammation resolution response. We sought to determine whether these processes might be linked through Treg-cell-mediated enhancement of efferocytosis. In zymosan-induced peritonitis and lipopolysaccharide-induced lung injury, Treg cells increased early in resolution, and Treg cell depletion decreased efferocytosis. Read More
Immunity 2018 Oct 2;49(4):709-724.e8. Epub 2018 Oct 2.
Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Mucosal Immunology Studies Team (MIST), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20982, USA; Program for Inflammatory and Cardiovascular Disorders, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), 08003 Barcelona, Spain; Catalan Institute for Research and Advanced Studies (ICREA), 08003 Barcelona, Spain. Electronic address:
B cells thwart antigenic aggressions by releasing immunoglobulin M (IgM), IgG, IgA, and IgE, which deploy well-understood effector functions. In contrast, the role of secreted IgD remains mysterious. We found that some B cells generated IgD-secreting plasma cells following early exposure to external soluble antigens such as food proteins. Read More
Immunity 2018 Oct 2;49(4):695-708.e4. Epub 2018 Oct 2.
Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address:
B cells can present antigens to CD4 T cells, but it is thought that dendritic cells (DCs) are the primary initiators of naive CD4 T cell responses. Nanoparticles, including virus-like particles (VLPs), are attractive candidates as carriers for vaccines and drug delivery. Using RNA phage Qβ-derived VLP (Qβ-VLP) as a model antigen, we found that antigen-specific B cells were the dominant antigen-presenting cells that initiated naive CD4 T cell activation. Read More
Immunity 2018 Oct 25;49(4):654-665.e5. Epub 2018 Sep 25.
Dynamics of Immune Responses Unit, Institut Pasteur, 75015 Paris, France; INSERM U1223, 75015 Paris, France. Electronic address:
Recruitment of immune cells with antimicrobial activities is essential to fight local infections but has the potential to trigger immunopathology. Whether the immune system has the ability to sense inflammation intensity and self-adjust accordingly to limit tissue damage remains to be fully established. During local infection with an intracellular pathogen, we have shown that nitric oxide (NO) produced by recruited monocyte-derived cells was essential to limit inflammation and cell recruitment. Read More
Immunity 2018 Sep;49(3):515-530.e5
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. Electronic address:
Fungi represent a significant proportion of the gut microbiota. Aberrant immune responses to fungi are frequently observed in inflammatory bowel diseases (IBD) and colorectal cancer (CRC), and mutations in the fungal-sensing pathways are associated with the pathogenesis of IBD. Fungal recognition receptors trigger downstream signaling via the common adaptor protein CARD9 and the kinase SYK. Read More
Immunity 2018 Sep;49(3):504-514.e4
Institute for Immunology, Tsinghua University School of Medicine, Tsinghua, Beijing 100084, China; Tsinghua University-Peking University Joint Center for Life Sciences, Beijing 100084, China. Electronic address:
The adaptor protein CARD9 links detection of fungi by surface receptors to the activation of the NF-κB pathway. Mice deficient in CARD9 exhibit dysbiosis and are more susceptible to colitis. Here we examined the impact of Card9 deficiency in the development of colitis-associated colon cancer (CAC). Read More
Immunity 2018 Sep;49(3):477-489.e7
MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, OX3 9DS, UK. Electronic address:
Adaptive immunity involves the development of bespoke antibodies in germinal centers (GCs) through immunoglobulin somatic hypermutation (SHM) in GC dark zones (DZs) and clonal selection in light zones (LZs). Accurate selection requires that cells fully replace surface B cell receptors (BCRs) following SHM, but whether this happens before LZ entry is not clear. We found that most GC B cells degrade pre-SHM receptors before leaving the DZ, and that B cells acquiring crippling mutations during SHM rarely reached the LZ. Read More
Immunity 2018 Sep;49(3):397-412
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Electronic address:
Successful pregnancy requires carefully-coordinated communications between the mother and fetus. Immune cells and cytokine signaling pathways participate as mediators of these communications to promote healthy pregnancy. At the same time, certain infections or inflammatory conditions in pregnant mothers cause severe disease and have detrimental impacts on the developing fetus. Read More