4,740 results match your criteria Immunity[Journal]


The Dendritic Cell Strikes Back.

Immunity 2019 Feb;50(2):533

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http://dx.doi.org/10.1016/j.immuni.2019.01.022DOI Listing
February 2019
1 Read

Chemokine Receptor Redundancy and Specificity Are Context Dependent.

Immunity 2019 Feb;50(2):378-389.e5

Chemokine Research Group, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TT, UK. Electronic address:

Currently, we lack an understanding of the individual and combinatorial roles for chemokine receptors in the inflammatory process. We report studies on mice with a compound deletion of Ccr1, Ccr2, Ccr3, and Ccr5, which together control monocytic and eosinophilic recruitment to resting and inflamed sites. Analysis of resting tissues from these mice, and mice deficient in each individual receptor, provides clear evidence for redundant use of these receptors in establishing tissue-resident monocytic cell populations. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.01.009DOI Listing
February 2019

Human FOXP3 Regulatory T Cell Heterogeneity and Function in Autoimmunity and Cancer.

Immunity 2019 Feb;50(2):302-316

Laboratory of Experimental Immunology, Immunology Frontier Research Center, Osaka University, Suita 565-0871, Japan; Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan. Electronic address:

Regulatory T (Treg) cells expressing the transcription factor Foxp3 have a critical role in the maintenance of immune homeostasis and prevention of autoimmunity. Recent advances in single cell analyses have revealed a range of Treg cell activation and differentiation states in different human pathologies. Here we review recent progress in the understanding of human Treg cell heterogeneity and function. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.01.020DOI Listing
February 2019

Emerging Principles in Myelopoiesis at Homeostasis and during Infection and Inflammation.

Immunity 2019 Feb;50(2):288-301

Myeloid Cell Biology, LIMES Institute, University of Bonn, 53115 Bonn, Germany. Electronic address:

Myelopoiesis ensures the steady state of the myeloid cell compartment. Technological advances in fate mapping and genetic engineering, as well as the advent of single cell RNA-sequencing, have highlighted the heterogeneity of the hematopoietic system and revealed new concepts in myeloid cell ontogeny. These technologies are also shedding light on mechanisms of myelopoiesis at homeostasis and at different phases of infection and inflammation, illustrating important feedback loops between affected tissues and the bone marrow. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.01.019DOI Listing
February 2019

The Secret Life of IgE-Producing Cells.

Immunity 2019 Feb;50(2):285-287

Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, New York University School of Medicine, New York, NY 10016, USA; Department of Cell Biology, New York University School of Medicine, New York, NY 10016, USA. Electronic address:

IgE antibodies are essential mediators of allergies. In a recent study in Science, Croote et al. (2018) characterize IgE cells isolated from individuals allergic to peanuts. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.01.018DOI Listing
February 2019

Playing Chess with HIV.

Authors:
Andrew B Ward

Immunity 2019 Feb;50(2):283-285

Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address:

HIV envelope glycoprotein (Env) exhibits extreme antigenic variation that can be countered by an amazing class of immunoglobulins known as broadly neutralizing antibodies. Dingens et al. (2019) use saturating mutagenesis of Env to play out all of the potential bnAb escape strategies and in doing so define the functional epitopes of these important vaccine and immunotherapeutic targets. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.01.011DOI Listing
February 2019

Live or Let Die: T Cell Survival in Cancer Immunotherapy.

Immunity 2019 Feb;50(2):280-282

Laboratory of Experimental Dermatology, Department of Dermatology, Otto-von-Guericke University, Magdeburg, Germany. Electronic address:

Combination immune checkpoint blockade targeting CTLA-4 and PD-1 is thought to reinvigorate exhausted T cells better than monotherapies. In this issue of Immunity, Pai et al. (2019) show that, in the setting of low tumor burden, this combination regimen promotes interferon-γ-dependent T cell hyperactivation and death and thus favors tumor progression. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.01.016DOI Listing
February 2019

A Dual Role for TNF-Producing T Cells in the Fetal Intestine.

Immunity 2019 Feb;50(2):278-280

Department of Medicine 1, Translational Research Center and Kussmaul Campus for Medical Research, University of Erlangen-Nürnberg, Erlangen, Germany. Electronic address:

The role of tumor necrosis factor (TNF) in the fetal intestine is poorly understood. In this issue of Immunity, Schreurs et al. (2019) identify important roles of TNF-producing T cells as both regulators of gut development and potential inducers of colitis. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.01.017DOI Listing
February 2019

Butyrate Makes Macrophages "Go Nuclear" against Bacterial Pathogens.

Immunity 2019 Feb;50(2):275-278

Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, 665 Huntington Ave, Boston, MA 02115, USA. Electronic address:

Butyrate is a microbial metabolite with pleiotropic effects. Schulthess et al. (2019) report that butyrate preconditioning of macrophages enhances their anti-bacterial preparedness by inducing anti-microbial proteins that restrict bacterial growth. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.01.015DOI Listing
February 2019

Leukocyte Trafficking: Time to Take Time Seriously.

Immunity 2019 Feb;50(2):273-275

William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK. Electronic address:

Leukocyte trafficking is a key component of steady-state tissue homing and in mounting an inflammatory response. Two recent publications in Immunity by He et al. (2018) and Adrover et al. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.01.013DOI Listing
February 2019

A Macrophage-Pericyte Axis Directs Tissue Restoration via Amphiregulin-Induced Transforming Growth Factor Beta Activation.

Immunity 2019 Feb 6. Epub 2019 Feb 6.

Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3FL, UK. Electronic address:

The epidermal growth factor receptor ligand Amphiregulin has a well-documented role in the restoration of tissue homeostasis after injury; however, the mechanism by which Amphiregulin contributes to wound repair remains unknown. Here we show that Amphiregulin functioned by releasing bioactive transforming growth factor beta (TGF-β) from latent complexes via integrin-α activation. Using acute injury models in two different tissues, we found that by inducing TGF-β activation on mesenchymal stromal cells (pericytes), Amphiregulin induced their differentiation into myofibroblasts, thereby selectively contributing to the restoration of vascular barrier function within injured tissue. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.01.008DOI Listing
February 2019

O-GlcNAc Transferase Suppresses Inflammation and Necroptosis by Targeting Receptor-Interacting Serine/Threonine-Protein Kinase 3.

Immunity 2019 Feb 5. Epub 2019 Feb 5.

Department of Microbial Infection and Immunity, Infectious Disease Institute, The Ohio State University Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA. Electronic address:

Elevated glucose metabolism in immune cells represents a hallmark feature of many inflammatory diseases, such as sepsis. However, the role of individual glucose metabolic pathways during immune cell activation and inflammation remains incompletely understood. Here, we demonstrate a previously unrecognized anti-inflammatory function of the O-linked β-N-acetylglucosamine (O-GlcNAc) signaling associated with the hexosamine biosynthesis pathway (HBP). Read More

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https://linkinghub.elsevier.com/retrieve/pii/S10747613193003
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http://dx.doi.org/10.1016/j.immuni.2019.01.007DOI Listing
February 2019
2 Reads

Specific Decrease in B-Cell-Derived Extracellular Vesicles Enhances Post-Chemotherapeutic CD8 T Cell Responses.

Immunity 2019 Feb 6. Epub 2019 Feb 6.

Institute of Immunology and Department of Orthopaedics of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China. Electronic address:

Systemic immunosuppression greatly affects the chemotherapeutic antitumor effect. Here, we showed that CD19 extracellular vesicles (EVs) from B cells through CD39 and CD73 vesicle-incorporated proteins hydrolyzed ATP from chemotherapy-treated tumor cells into adenosine, thus impairing CD8 T cell responses. Serum CD19 EVs were increased in tumor-bearing mice and patients. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.01.010DOI Listing
February 2019
2 Reads

Spatial and Temporal Mapping of Human Innate Lymphoid Cells Reveals Elements of Tissue Specificity.

Immunity 2019 Feb 12;50(2):505-519.e4. Epub 2019 Feb 12.

Jill Roberts Institute for Research in Inflammatory Bowel Disease, Joan and Stanford I. Weill Department of Medicine, Weill Cornell Medicine, New York, NY, 10021, USA. Electronic address:

Innate lymphoid cells (ILC) play critical roles in regulating immunity, inflammation, and tissue homeostasis in mice. However, limited access to non-diseased human tissues has hindered efforts to profile anatomically-distinct ILCs in humans. Through flow cytometric and transcriptional analyses of lymphoid, mucosal, and metabolic tissues from previously healthy human organ donors, here we have provided a map of human ILC heterogeneity across multiple anatomical sites. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.01.012DOI Listing
February 2019
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Human Fetal TNF-α-Cytokine-Producing CD4 Effector Memory T Cells Promote Intestinal Development and Mediate Inflammation Early in Life.

Immunity 2019 Feb 12;50(2):462-476.e8. Epub 2019 Feb 12.

Department of Experimental Immunology, Amsterdam Infection & Immunity Institute, Amsterdam University Medical Center, University of Amsterdam, Amsterdam 1105 AZ, the Netherlands; Department of Pediatrics, Emma Children's Hospital, Amsterdam University Medical Center, University of Amsterdam, Amsterdam 1105 AZ, the Netherlands; Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg 20251, Germany. Electronic address:

Although the fetal immune system is considered tolerogenic, preterm infants can suffer from severe intestinal inflammation, including necrotizing enterocolitis (NEC). Here, we demonstrate that human fetal intestines predominantly contain tumor necrosis factor-α (TNF-α)CD4CD69 T effector memory (Tem) cells. Single-cell RNA sequencing of fetal intestinal CD4 T cells showed a T helper 1 phenotype and expression of genes mediating epithelial growth and cell cycling. Read More

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http://dx.doi.org/10.1016/j.immuni.2018.12.010DOI Listing
February 2019

The ATP-Binding Cassette Gene ABCF1 Functions as an E2 Ubiquitin-Conjugating Enzyme Controlling Macrophage Polarization to Dampen Lethal Septic Shock.

Immunity 2019 Feb 12;50(2):418-431.e6. Epub 2019 Feb 12.

Michael Smith Laboratories, University of British Columbia (UBC), 2185 East Mall, Vancouver, BC, V6T 1Z4, Canada; The Vancouver Prostate Centre, 2660 Oak Street, Vancouver, BC V6H 3Z6, Canada; Department of Microbiology and Immunology, UBC, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada; Centre for Blood Research, UBC, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada; Department of Zoology, UBC, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada; Department of Medical Genetics, UBC, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada; Djavad Mowafaghian Centre for Brain Health, 2215 Wesbrook Mall, Vancouver, BC V6T 2B5, Canada. Electronic address:

Sepsis is a bi-phasic inflammatory disease that threatens approximately 30 million lives and claims over 14 million annually, yet little is known regarding the molecular switches and pathways that regulate this disease. Here, we have described ABCF1, an ATP-Binding Cassette (ABC) family member protein, which possesses an E2 ubiquitin enzyme activity, through which it controls the Lipopolysaccharide (LPS)- Toll-like Receptor-4 (TLR4) mediated gram-negative insult by targeting key proteins for K63-polyubiquitination. Ubiquitination by ABCF1 shifts the inflammatory profile from an early phase MyD88-dependent to a late phase TRIF-dependent signaling pathway, thereby regulating TLR4 endocytosis and modulating macrophage polarization from M1 to M2 phase. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.01.014DOI Listing
February 2019
1 Read

Dengue Virus Immunity Increases Zika Virus-Induced Damage during Pregnancy.

Immunity 2019 Jan 30. Epub 2019 Jan 30.

Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address:

Zika virus (ZIKV) has recently been associated with birth defects and pregnancy loss after maternal infection. Because dengue virus (DENV) and ZIKV co-circulate, understanding the role of antibody-dependent enhancement in the context of pregnancy is critical. Here, we showed that the presence of DENV-specific antibodies in ZIKV-infected pregnant mice significantly increased placental damage, fetal growth restriction, and fetal resorption. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.01.005DOI Listing
January 2019
2 Reads

The Histone Methyltransferase SETDB1 Controls T Helper Cell Lineage Integrity by Repressing Endogenous Retroviruses.

Immunity 2019 Jan 31. Epub 2019 Jan 31.

Center for Physiopathology of Toulouse Purpan, Centre National de la Recherche Scientifique, INSERM, Université Paul Sabatier Toulouse III, Toulouse, France. Electronic address:

Upon activation, naive CD4 T cells differentiate into distinct T cell subsets via processes reliant on epigenetically regulated, lineage-specific developmental programs. Here, we examined the function of the histone methyltransferase SETDB1 in T helper (Th) cell differentiation. Setdb1 naive CD4 T cells exhibited exacerbated Th1 priming, and when exposed to a Th1-instructive signal, Setdb1 Th2 cells crossed lineage boundaries and acquired a Th1 phenotype. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.01.003DOI Listing
January 2019

Clonal Deletion of Tumor-Specific T Cells by Interferon-γ Confers Therapeutic Resistance to Combination Immune Checkpoint Blockade.

Immunity 2019 Feb 5;50(2):477-492.e8. Epub 2019 Feb 5.

Department of Hematology and Oncology, University of California, San Francisco, San Francisco, CA 94143, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address:

Resistance to checkpoint-blockade treatments is a challenge in the clinic. We found that although treatment with combined anti-CTLA-4 and anti-PD-1 improved control of established tumors, this combination compromised anti-tumor immunity in the low tumor burden (LTB) state in pre-clinical models as well as in melanoma patients. Activated tumor-specific T cells expressed higher amounts of interferon-γ (IFN-γ) receptor and were more susceptible to apoptosis than naive T cells. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.01.006DOI Listing
February 2019
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Survival of Single Positive Thymocytes Depends upon Developmental Control of RIPK1 Kinase Signaling by the IKK Complex Independent of NF-κB.

Immunity 2019 Feb 5;50(2):348-361.e4. Epub 2019 Feb 5.

Division of Infection and Immunity, UCL Institute of Immunity and Transplantation, Royal Free Hospital, Rowland Hill Street, London NW3 2PF, UK. Electronic address:

NF-κB (nuclear factor κB) signaling is considered critical for single positive (SP) thymocyte development because loss of upstream activators of NF-κB, such as the IKK complex, arrests their development. We found that the compound ablation of RelA, cRel, and p50, required for canonical NF-κB transcription, had no impact upon thymocyte development. While IKK-deficient thymocytes were acutely sensitive to tumor necrosis factor (TNF)-induced cell death, Rel-deficient cells remained resistant, calling into question the importance of NF-κB as the IKK target required for thymocyte survival. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.01.004DOI Listing
February 2019

Single-Cell Transcriptomics of Regulatory T Cells Reveals Trajectories of Tissue Adaptation.

Immunity 2019 Feb 5;50(2):493-504.e7. Epub 2019 Feb 5.

Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK; Theory of Condensed Matter, Cavendish Laboratory, Department of Physics, University of Cambridge, Cambridge, UK; European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, UK. Electronic address:

Non-lymphoid tissues (NLTs) harbor a pool of adaptive immune cells with largely unexplored phenotype and development. We used single-cell RNA-seq to characterize 35,000 CD4 regulatory (Treg) and memory (Tmem) T cells in mouse skin and colon, their respective draining lymph nodes (LNs) and spleen. In these tissues, we identified Treg cell subpopulations with distinct degrees of NLT phenotype. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.01.001DOI Listing
February 2019
1 Read

The Lupus Susceptibility Locus Sgp3 Encodes the Suppressor of Endogenous Retrovirus Expression SNERV.

Immunity 2019 Feb 29;50(2):334-347.e9. Epub 2019 Jan 29.

Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Electronic address:

Elevated endogenous retrovirus (ERV) transcription and anti-ERV antibody reactivity are implicated in lupus pathogenesis. Overproduction of non-ecotropic ERV (NEERV) envelope glycoprotein gp70 and resultant nephritis occur in lupus-prone mice, but whether NEERV mis-expression contributes to lupus etiology is unclear. Here we identified suppressor of NEERV (Snerv) 1 and 2, Krüppel-associated box zinc-finger proteins (KRAB-ZFPs) that repressed NEERV by binding the NEERV long terminal repeat to recruit the transcriptional regulator KAP1. Read More

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http://dx.doi.org/10.1016/j.immuni.2018.12.022DOI Listing
February 2019
1 Read

Microbiota Sensing by Mincle-Syk Axis in Dendritic Cells Regulates Interleukin-17 and -22 Production and Promotes Intestinal Barrier Integrity.

Immunity 2019 Feb 29;50(2):446-461.e9. Epub 2019 Jan 29.

Immunobiology Laboratory, Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Melchor Fernández Almagro 3, Madrid 28029, Spain. Electronic address:

Production of interleukin-17 (IL-17) and IL-22 by T helper 17 (Th17) cells and group 3 innate lymphoid cells (ILC3s) in response to the gut microbiota ensures maintenance of intestinal barrier function. Here, we examined the mechanisms whereby the immune system detects microbiota in the steady state. A Syk-kinase-coupled signaling pathway in dendritic cells (DCs) was critical for commensal-dependent production of IL-17 and IL-22 by CD4 T cells. Read More

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http://dx.doi.org/10.1016/j.immuni.2018.12.020DOI Listing
February 2019
1 Read

A Neutrophil Timer Coordinates Immune Defense and Vascular Protection.

Immunity 2019 Feb 29;50(2):390-402.e10. Epub 2019 Jan 29.

Area of Developmental and Cell Biology, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximillians-Universität München. Electronic address:

Neutrophils eliminate pathogens efficiently but can inflict severe damage to the host if they over-activate within blood vessels. It is unclear how immunity solves the dilemma of mounting an efficient anti-microbial defense while preserving vascular health. Here, we identify a neutrophil-intrinsic program that enabled both. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.01.002DOI Listing
February 2019
3 Reads

Liver-Resident NK Cells Control Antiviral Activity of Hepatic T Cells via the PD-1-PD-L1 Axis.

Immunity 2019 Feb 29;50(2):403-417.e4. Epub 2019 Jan 29.

Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China; Institue of Immunology, University of Science and Technology of China, Hefei, Anhui 230027, China. Electronic address:

The tolerogenic microenvironment of the liver is associated with impaired hepatic T cell function. Here, we examined the contribution of liver-resident natural killer (LrNK) cells, a prominent hepatic NK cell compartment, to T cell antiviral responses in the liver. The number of virus-specific T cells increased in LrNK-cell-deficient mice during both acute and chronic lymphocytic choriomeningitis virus infection. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S10747613183057
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http://dx.doi.org/10.1016/j.immuni.2018.12.024DOI Listing
February 2019
6 Reads

An Antigenic Atlas of HIV-1 Escape from Broadly Neutralizing Antibodies Distinguishes Functional and Structural Epitopes.

Immunity 2019 Feb 29;50(2):520-532.e3. Epub 2019 Jan 29.

Basic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Howard Hughes Medical Institute, Seattle, WA 98109, USA. Electronic address:

Anti-HIV broadly neutralizing antibodies (bnAbs) have revealed vaccine targets on the virus's envelope (Env) protein and are themselves promising immunotherapies. The efficacy of bnAb-based therapies and vaccines depends in part on how readily the virus can escape neutralization. Although structural studies can define contacts between bnAbs and Env, only functional studies can define mutations that confer escape. Read More

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http://dx.doi.org/10.1016/j.immuni.2018.12.017DOI Listing
February 2019

A Mutation in the Transcription Factor Foxp3 Drives T Helper 2 Effector Function in Regulatory T Cells.

Immunity 2019 Feb 29;50(2):362-377.e6. Epub 2019 Jan 29.

Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA; Sean N. Parker Autoimmune Research Laboratory, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address:

Regulatory T (Treg) cells maintain immune tolerance through the master transcription factor forkhead box P3 (FOXP3), which is crucial for Treg cell function and homeostasis. We identified an IPEX (immune dysregulation polyendocrinopathy enteropathy X-linked) syndrome patient with a FOXP3 mutation in the domain swap interface of the protein. Recapitulation of this Foxp3 variant in mice led to the development of an autoimmune syndrome consistent with an unrestrained T helper type 2 (Th2) immune response. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S10747613183056
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http://dx.doi.org/10.1016/j.immuni.2018.12.016DOI Listing
February 2019
4 Reads
21.561 Impact Factor

Cell-Type-Specific Interleukin 1 Receptor 1 Signaling in the Brain Regulates Distinct Neuroimmune Activities.

Immunity 2019 Feb 22;50(2):317-333.e6. Epub 2019 Jan 22.

Institute for Behavioral Medicine Research, College of Medicine, The Ohio State University, Columbus, OH 43210, USA; Division of Biosciences, College of Dentistry, The Ohio State University, Columbus, OH 43210, USA. Electronic address:

Interleukin-1 (IL-1) signaling is important for multiple potentially pathogenic processes in the central nervous system (CNS), but the cell-type-specific roles of IL-1 signaling are unclear. We used a genetic knockin reporter system in mice to track and reciprocally delete or express IL-1 receptor 1 (IL-1R1) in specific cell types, including endothelial cells, ventricular cells, peripheral myeloid cells, microglia, astrocytes, and neurons. We found that endothelial IL-1R1 was necessary and sufficient for mediating sickness behavior and drove leukocyte recruitment to the CNS and impaired neurogenesis, whereas ventricular IL-1R1 was critical for monocyte recruitment to the CNS. Read More

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http://dx.doi.org/10.1016/j.immuni.2018.12.012DOI Listing
February 2019
1 Read

The Short Chain Fatty Acid Butyrate Imprints an Antimicrobial Program in Macrophages.

Immunity 2019 Feb 23;50(2):432-445.e7. Epub 2019 Jan 23.

Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Roosevelt Drive, 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:

Host microbial cross-talk is essential to maintain intestinal homeostasis. However, maladaptation of this response through microbial dysbiosis or defective host defense toward invasive intestinal bacteria can result in chronic inflammation. We have shown that macrophages differentiated in the presence of the bacterial metabolite butyrate display enhanced antimicrobial activity. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S10747613183056
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http://dx.doi.org/10.1016/j.immuni.2018.12.018DOI Listing
February 2019
3 Reads

Defining Dysbiosis in Inflammatory Bowel Disease.

Immunity 2019 Jan;50(1):8-10

Center of Allergy and Environment (ZAUM), Helmholtz Center and Technical University Munich, Munich, Germany. Electronic address:

In this issue of Immunity, Britton et al. (2019) demonstrate that the colonization of germ-free mice with microbiotas from inflammatory bowel disease patients induces an altered ratio of RORγt regulatory T cells to T(h17) effector cells and recapitulates human disease severity in colitis-susceptible mice. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S10747613183057
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http://dx.doi.org/10.1016/j.immuni.2018.12.028DOI Listing
January 2019
4 Reads

The First Shall (Be) Last: Understanding Durable T Cell Responses in Immunotherapy.

Immunity 2019 Jan;50(1):6-8

Division of Molecular Oncology and Immunology, the Netherlands Cancer Institute, Oncode Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands. Electronic address:

Efforts to understand how cancer immunotherapy restores anti-tumor T cell responses have largely concentrated on assessing the reactivation of dysfunctional T cells. In this issue of Immunity, Kurtulus et al. (2019) and Siddiqui et al. Read More

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http://dx.doi.org/10.1016/j.immuni.2018.12.029DOI Listing
January 2019

Plasmacytoid Dendritic Cells: Development, Regulation, and Function.

Authors:
Boris Reizis

Immunity 2019 Jan;50(1):37-50

Department of Pathology and Department of Medicine, New York University School of Medicine, New York, NY 10016, USA. Electronic address:

Plasmacytoid dendritic cells (pDCs) are a unique sentinel cell type that can detect pathogen-derived nucleic acids and respond with rapid and massive production of type I interferon. This review summarizes our current understanding of pDC biology, including transcriptional regulation, heterogeneity, role in antiviral immune responses, and involvement in immune pathology, particularly in autoimmune diseases, immunodeficiency, and cancer. We also highlight the remaining gaps in our knowledge and important questions for the field, such as the molecular basis of unique interferon-producing capacity of pDCs. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S10747613183057
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http://dx.doi.org/10.1016/j.immuni.2018.12.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6342491PMC
January 2019
3 Reads

Coronin-1, King of Alloimmunity.

Authors:
Mandy L Ford

Immunity 2019 Jan;50(1):3-5

Emory Transplant Center and Department of Surgery, Emory University, Atlanta, GA, USA. Electronic address:

Defining pathways that differentially regulate graft-reactive versus anti-microbial T cell responses could facilitate more precise manipulation of immune responses in the context of organ and tissue transplantation. Here, Jayachandran et al. (2019) identify a coronin-1-PDE4-cAMP axis that, when perturbed, results in the induction of transplantation tolerance while maintaining anti-microbial immunity. Read More

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http://dx.doi.org/10.1016/j.immuni.2018.12.030DOI Listing
January 2019
5 Reads

Microbiotas from Humans with Inflammatory Bowel Disease Alter the Balance of Gut Th17 and RORγt Regulatory T Cells and Exacerbate Colitis in Mice.

Immunity 2019 Jan;50(1):212-224.e4

Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address:

Microbiota are thought to influence the development and progression of inflammatory bowel disease (IBD), but determining generalizable effects of microbiota on IBD etiology requires larger-scale functional analyses. We colonized germ-free mice with intestinal microbiotas from 30 healthy and IBD donors and determined the homeostatic intestinal T cell response to each microbiota. Compared to microbiotas from healthy donors, transfer of IBD microbiotas into germ-free mice increased numbers of intestinal Th17 cells and Th2 cells and decreased numbers of RORγt Treg cells. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S10747613183056
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http://dx.doi.org/10.1016/j.immuni.2018.12.015DOI Listing
January 2019
9 Reads

Perinatal Interactions between the Microbiome, Immunity, and Neurodevelopment.

Immunity 2019 Jan;50(1):18-36

Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address:

The microbiome modulates host immune function across the gastrointestinal tract, peripheral lymphoid organs, and central nervous system. In this review, we highlight emerging evidence that microbial effects on select immune phenotypes arise developmentally, where the maternal and neonatal microbiome influence immune cell ontogeny in the offspring during gestation and early postnatal life. We further discuss roles for the perinatal microbiome and early-life immunity in regulating normal neurodevelopmental processes. Read More

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http://dx.doi.org/10.1016/j.immuni.2018.11.016DOI Listing
January 2019
10 Reads

Cell-Type-Specific Responses to Interleukin-1 Control Microbial Invasion and Tumor-Elicited Inflammation in Colorectal Cancer.

Immunity 2019 Jan;50(1):166-180.e7

Cancer Prevention and Control Program, Fox Chase Cancer Center, Philadelphia, PA, 19111, USA. Electronic address:

Chronic inflammation drives the progression of colorectal cancer (CRC). Increased expression of interleukin (IL)-17A is associated with poor prognosis, and IL-17A blockade curbs tumor progression in preclinical models of CRC. Here we examined the impact of IL-1 signaling, a key regulator of the IL-17 pathway, in different cell types within the CRC microenvironment. Read More

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http://dx.doi.org/10.1016/j.immuni.2018.11.015DOI Listing
January 2019
5 Reads

Defying Death: The (W)hole Truth about the Fate of GSDMD Pores.

Immunity 2019 Jan;50(1):15-17

Harvard Medical School and Division of Gastroenterology, Boston Children's Hospital, Boston, MA, USA; Program in Immunology, Harvard Medical School, Boston, MA, USA. Electronic address:

Pyroptosis is an inflammatory cell death response initiated by supramolecular organizing centers known as inflammasomes. In a recent issue of Science, Rühl et al. (2018) challenge the paradigm that inflammasome signaling necessitates pyroptosis by demonstrating that ESCRTIII-dependent membrane repair can delay or prevent gasdermin D-mediated cell death. Read More

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http://dx.doi.org/10.1016/j.immuni.2018.12.032DOI Listing
January 2019

Fever Promotes T Lymphocyte Trafficking via a Thermal Sensory Pathway Involving Heat Shock Protein 90 and α4 Integrins.

Immunity 2019 Jan;50(1):137-151.e6

State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China. Electronic address:

Fever is an evolutionarily conserved response that confers survival benefits during infection. However, the underlying mechanism remains obscure. Here, we report that fever promoted T lymphocyte trafficking through heat shock protein 90 (Hsp90)-induced α4 integrin activation and signaling in T cells. Read More

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http://dx.doi.org/10.1016/j.immuni.2018.11.013DOI Listing
January 2019
5 Reads

Gaining Weight: Insulin-Eating Islet Macrophages.

Immunity 2019 Jan;50(1):13-15

Department of Comparative Medicine and Yale Center for Research on Aging, New Haven, CT 06520, USA; Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA. Electronic address:

The role of the immune system in homeostasis of pancreatic β cells in type 2 diabetes mellitus is poorly characterized. In a recent issue of Cell Metabolism, Ying et al. (2018) report that two subpopulations of macrophages expand during obesity to impair β cell function. Read More

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http://dx.doi.org/10.1016/j.immuni.2018.12.026DOI Listing
January 2019
3 Reads

Demystifying Microglia: And Now the Work Begins.

Immunity 2019 Jan;50(1):11-13

Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA; Neuroscience Graduate Program, University of California, San Francisco, San Francisco, CA, USA. Electronic address:

Microglia actively shape the developing brain, but their transcriptional diversity is not well understood. Complementary studies by Hammond et al. (2018) and Li et al. Read More

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http://dx.doi.org/10.1016/j.immuni.2018.12.025DOI Listing
January 2019

Retinoic Acid Receptor Alpha Represses a Th9 Transcriptional and Epigenomic Program to Reduce Allergic Pathology.

Immunity 2019 Jan;50(1):106-120.e10

Molecular Immunology and Inflammation Branch, NIAMS, NIH, Rockville, MD 20892, USA.

CD4 T helper (Th) differentiation is regulated by diverse inputs, including the vitamin A metabolite retinoic acid (RA). RA acts through its receptor RARα to repress transcription of inflammatory cytokines, but is also essential for Th-mediated immunity, indicating complex effects of RA on Th specification and the outcome of the immune response. We examined the impact of RA on the genome-wide transcriptional response during Th differentiation to multiple subsets. Read More

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http://dx.doi.org/10.1016/j.immuni.2018.12.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6338086PMC
January 2019
4 Reads
21.561 Impact Factor

RIPK3: Beyond Necroptosis.

Immunity 2019 Jan;50(1):1-3

Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Center for Microbial Pathogenesis, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA; R. K. Mellon Institute for Pediatric Research, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA 15219, USA. Electronic address:

In this issue of Immunity, Daniels et al. (2019) demonstrate that RIPK3 signaling limits Zika virus (ZIKV) infection in the central nervous system independently of its function in necroptosis by promoting itaconate production in infected neurons, thereby revealing a neuron-specific mechanism of metabolite-mediated ZIKV control. Read More

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http://dx.doi.org/10.1016/j.immuni.2018.12.031DOI Listing
January 2019
3 Reads

The Emergence and Functional Fitness of Memory CD4 T Cells Require the Transcription Factor Thpok.

Immunity 2019 Jan 9;50(1):91-105.e4. Epub 2019 Jan 9.

Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address:

Memory CD4 T cells mediate long-term immunity, and their generation is a key objective of vaccination strategies. However, the transcriptional circuitry controlling the emergence of memory cells from early CD4 antigen-responders remains poorly understood. Here, using single-cell RNA-seq to study the transcriptome of virus-specific CD4 T cells, we identified a gene signature that distinguishes potential memory precursors from effector cells. Read More

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http://dx.doi.org/10.1016/j.immuni.2018.12.019DOI Listing
January 2019
12 Reads
21.561 Impact Factor

The Nucleotide Sensor ZBP1 and Kinase RIPK3 Induce the Enzyme IRG1 to Promote an Antiviral Metabolic State in Neurons.

Immunity 2019 Jan 8;50(1):64-76.e4. Epub 2019 Jan 8.

Department of Immunology, University of Washington, Seattle, WA 98109, USA; Center for Innate Immunity and Immune Disease, University of Washington, Seattle, WA 98109, USA. Electronic address:

As long-lived post-mitotic cells, neurons employ unique strategies to resist pathogen infection while preserving cellular function. Here, using a murine model of Zika virus (ZIKV) infection, we identified an innate immune pathway that restricts ZIKV replication in neurons and is required for survival upon ZIKV infection of the central nervous system (CNS). We found that neuronal ZIKV infection activated the nucleotide sensor ZBP1 and the kinases RIPK1 and RIPK3, core components of virus-induced necroptotic cell death signaling. Read More

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http://dx.doi.org/10.1016/j.immuni.2018.11.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6342485PMC
January 2019
6 Reads

Oligoadenylate-Synthetase-Family Protein OASL Inhibits Activity of the DNA Sensor cGAS during DNA Virus Infection to Limit Interferon Production.

Immunity 2019 Jan 8;50(1):51-63.e5. Epub 2019 Jan 8.

Cancer Virology Program, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA 15213, USA; Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 15219, USA. Electronic address:

Interferon-inducible human oligoadenylate synthetase-like (OASL) and its mouse ortholog, Oasl2, enhance RNA-sensor RIG-I-mediated type I interferon (IFN) induction and inhibit RNA virus replication. Here, we show that OASL and Oasl2 have the opposite effect in the context of DNA virus infection. In Oasl2 mice and OASL-deficient human cells, DNA viruses such as vaccinia, herpes simplex, and adenovirus induced increased IFN production, which resulted in reduced virus replication and pathology. Read More

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http://dx.doi.org/10.1016/j.immuni.2018.12.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6342484PMC
January 2019
1 Read
21.561 Impact Factor

Impaired Tumor-Necrosis-Factor-α-driven Dendritic Cell Activation Limits Lipopolysaccharide-Induced Protection from Allergic Inflammation in Infants.

Immunity 2019 Jan 8;50(1):225-240.e4. Epub 2019 Jan 8.

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

Infants have a higher risk of developing allergic asthma than adults. However, the underlying mechanism remains unknown. We show here that sensitization of mice with house-dust mites (HDMs) in the presence of low-dose lipopolysaccharide (LPS) prevented T helper 2 (Th2) cell allergic responses in adult, but not infant, mice. Read More

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http://dx.doi.org/10.1016/j.immuni.2018.11.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6335154PMC
January 2019
5 Reads

Intratumoral Tcf1PD-1CD8 T Cells with Stem-like Properties Promote Tumor Control in Response to Vaccination and Checkpoint Blockade Immunotherapy.

Immunity 2019 Jan 8;50(1):195-211.e10. Epub 2019 Jan 8.

Department of Oncology UNIL CHUV, University of Lausanne, 1066 Epalinges, Switzerland. Electronic address:

Checkpoint blockade mediates a proliferative response of tumor-infiltrating CD8 T lymphocytes (TILs). The origin of this response has remained elusive because chronic activation promotes terminal differentiation or exhaustion of tumor-specific T cells. Here we identified a subset of tumor-reactive TILs bearing hallmarks of exhausted cells and central memory cells, including expression of the checkpoint protein PD-1 and the transcription factor Tcf1. Read More

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http://dx.doi.org/10.1016/j.immuni.2018.12.021DOI Listing
January 2019
4 Reads
21.561 Impact Factor

Checkpoint Blockade Immunotherapy Induces Dynamic Changes in PD-1CD8 Tumor-Infiltrating T Cells.

Immunity 2019 Jan 8;50(1):181-194.e6. Epub 2019 Jan 8.

Evergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA. Electronic address:

An improved understanding of the anti-tumor CD8 T cell response after checkpoint blockade would enable more informed and effective therapeutic strategies. Here we examined the dynamics of the effector response of CD8 tumor-infiltrating lymphocytes (TILs) after checkpoint blockade therapy. Bulk and single-cell RNA profiles of CD8 TILs after combined Tim-3+PD-1 blockade in preclinical models revealed significant changes in the transcriptional profile of PD-1 TILs. Read More

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http://dx.doi.org/10.1016/j.immuni.2018.11.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6336113PMC
January 2019
28 Reads

Transcription Factor PU.1 Promotes Conventional Dendritic Cell Identity and Function via Induction of Transcriptional Regulator DC-SCRIPT.

Immunity 2019 Jan 2;50(1):77-90.e5. Epub 2019 Jan 2.

Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia. Electronic address:

Dendritic cells (DCs) are can be broadly divided into conventional (cDC) and plasmacytoid (pDC) subsets. Despite the importance of this lineage diversity, its genetic basis is not fully understood. We found that conditional ablation of the Ets-family transcription factor PU. Read More

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http://dx.doi.org/10.1016/j.immuni.2018.11.010DOI Listing
January 2019
5 Reads