Immune Regulation News Volume 10.48 | Dec 14 2018

TOP STORY

Self-Renewing Resident Cardiac Macrophages Limit Adverse Remodeling following Myocardial Infarction

The authors used fate mapping, parabiosis and single-cell transcriptomics to demonstrate that at steady state, TIMD4⁺LYVE1⁺MHC-II^loCCR2⁻ resident cardiac macrophages self-renew with negligible blood monocyte input. [Nat Immunol] Abstract

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The Transcription Factor c-Maf Is Essential for the Commitment of IL-17-Producing γδ T Cells

Scientists identified the transcription factor c-Maf as a universal regulator of Tγδ17 cell differentiation and maintenance. Maf deficiency caused an absolute lineage block at the immature CD24⁺CD45RB^lo γδ thymocyte stage, which revealed a critical checkpoint in the acquisition of effector functions. [Nat Immunol] Abstract

Microbiota-Induced TNF-Like Ligand 1A Drives Group 3 Innate Lymphoid Cell-Mediated Barrier Protection and Intestinal T Cell Activation during Colitis

Researchers found that adherent inflammatory bowel disease-associated microbiota induced TNF-like ligand 1A (TL1A) release from CX3CR1⁺ mononuclear phagocytes. Using cell-specific genetic deletion models, they identified an essential role for CX3CR1⁺mononuclear phagocyte-derived TL1A in driving group 3 innate lymphoid cell production of interleukin-22 and mucosal healing during acute colitis. [Immunity] Abstract | Graphical Abstract

Control of T_reg Cell Homeostasis and Immune Equilibrium by Lkb1 in Dendritic Cells

Investigators showed that the number of regulatory T (T_reg) cells was negatively regulated by the kinase Lkb1 in dendritic cells (DCs). Conditional knockout of the Lkb1 gene in DCs led to excessive T_reg cell expansion in multiple organs and dampened antigen-specific T cell immunity. [Nat Commun] Full Article

Defective Respiration and One-Carbon Metabolism Contribute to Impaired Naïve T Cell Activation in Aged Mice

Researchers report a systematic analysis of metabolism during young versus aged naïve T cell activation. They observed a decrease in the number and activation of naïve T cells isolated from aged mice. [Proc Natl Acad Sci USA] Full Article | Press Release

Magnitude of Therapeutic STING Activation Determines CD8⁺ T Cell-Mediated Anti-Tumor Immunity

In contrast to high-dose tumor ablative regimens that result in systemic S100 distribution, low-dose immunogenic regimens induce local activation of tumor-specific CD8⁺ effector T cells that are responsible for durable anti-tumor immunity and can be enhanced with checkpoint inhibitors. [Cell Rep] Full Article | Press Release | Graphical Abstract

Drp1 Controls Effective T Cell Immune-Surveillance by Regulating T Cell Migration, Proliferation, and cMyc-Dependent Metabolic Reprogramming

Scientists showed that the mitochondrial pro-fission protein Drp1 fosters migration and expansion of developing thymocytes both in vitro and in vivo. In addition, they found that Drp1 sustained in vitro clonal expansion and cMyc-dependent metabolic reprogramming upon activation, also regulating effector T cell numbers in vivo. [Cell Rep] Full Article | Graphical Abstract

Batf2 Differentially Regulates Tissue Immunopathology in Type 1 and Type 2 Diseases

In basic leucine zipper transcription factor 2 (Batf2)-deficient mice, infected with Mycobacterium tuberculosis or Listeria monocytogenes, mice survived and displayed reduced tissue pathology compared to infected control mice. Indeed, pulmonary inflammatory macrophage recruitment, pro-inflammatory cytokines and immune effectors were also decreased during tuberculosis. [Mucosal Immunol] Full Article

CCR2 Enhances CD25 Expression by FoxP3⁺ Regulatory T Cells and Regulates Their Abundance Independently of Chemotaxis and CCR2⁺ Myeloid Cells

Researchers report that CCR2 regulated Tregs beyond chemotaxis. They found that CCR2 deficiency reduced CD25 expression by FoxP3⁺ Treg cells. [Cell Mol Immunol] Abstract

CD19⁺IgM⁺ Cells Demonstrate Enhanced Therapeutic Efficacy in Type 1 Diabetes Mellitus

Investigators describe a protective effect on autoimmune diabetes and reduced destructive insulitis in NOD.scid recipients following splenocyte injections from diabetic NOD donors and sorted CD19⁺ cells compared with NOD.scid recipients receiving splenocytes alone. [JCI Insight] Full Article

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Cancer Immunoediting and Resistance to T Cell-Based Immunotherapy

The authors discuss how a deeper understanding of the mechanisms underlying the cancer immunoediting process can provide insight into the development of resistance to immunotherapies and the strategies that can be used to overcome such resistance. [Nat Rev Clin Oncol] Abstract

Immune Checkpoint Inhibitors: Recent Progress and Potential Biomarkers

Scientists discuss different predictive biomarkers for anti-PD-1/PD-L1 and anti-CTLA-4 inhibitors, including immune cells, PD-L1 overexpression, neoantigens, and genetic and epigenetic signatures. [Exp Mol Med] Full Article

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Lilly and AC Immune Announce License and Collaboration Agreement

Eli Lilly and Company and AC Immune SA announced that the two companies have signed a license and collaboration agreement to research and develop tau aggregation inhibitor small molecules for the potential treatment of Alzheimer’s disease and other neurodegenerative diseases. [Eli Lilly and Company] Press Release

Omeros Announces Research Collaboration with University of Cambridge

Omeros Corporation announced that it has entered into a research collaboration with the University of Cambridge, establishing the Omeros Center at Cambridge for Complement and Inflammation Research. [Omeros Corporation] Press Release

WuXi Biologics Announced Exclusive Discovery Research with Brii Biosciences for Novel Bispecific Antibody Immunotherapeutics

WuXi Biologics announced a strategic collaboration with Brii Biosciences, an innovative biotechnology company operates in China and the US, focusing on accelerating innovation and optimizing access to serve the need of Chinese patients and public health, to discover and develop bispecific antibodies to treat infectious diseases and other immunologic disorders. [WuXi Biologics] Press Release

The End of DACA Would Be a Blow to Science

With the end of Deferred Action for Childhood Arrivals (DACA), undocumented scientists will lose what few protections they currently have under immigrant law, lose their access to their scientific research, and once again live in fear, as they are caught in legal limbo. [Scientific American] Editorial

South Korean Scientists Protest Treatment of University President Accused of Misusing Funds

Researchers in South Korea have criticized the nation’s science ministry for its handling of an investigation into the president of the Korea Advanced Institute of Science and Technology (KAIST) in Daejon, the country’s top technical university. The science ministry alleges that KAIST leader Shin Sung-Chul made illegal payments to a California lab, but many scientists see a political purge. [Nature News] Editorial

NIH Report Scrutinizes Role of China in Theft of U.S. Scientific Research

Institutions across the U.S. may have fallen victim to a tiny fraction of foreign researchers who worked to feed American intellectual property to their home countries, an advisory committee to the National Institutes of Health (NIH) found in a report. [STAT News] Editorial

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NEW Supervisor – Transfusion Medicine – Immune, Progenitor, & Cell Therapy (Mayo Clinic-Rochester)

Research Technologist – Immunology (STEMCELL Technologies Inc.)

Assistant/Associate or Professor – Cancer Immunotherapy/Tumor Immunology (University of California, Irvine)

Postdoctoral Fellow/Research Associate – Immunology (Turnstone Biologics Inc.)

Postdoctoral Position – Immunology (Ludwig-Maximilians-Universität)

Postdoctoral Position – Natural Killer Cells (The Scripps Research Institute)

Faculty Positions – Translational Immunology (University of Miami)

Postdoctoral Position – Immunology and Ion Channel Function (New York University School of Medicine)

PhD Position – Cancer Immunotherapy (Helmholtz Zentrum München)

Tenure/Tenure Track Faculty Position – Immunology (Wayne State University)

Postdoctoral Fellowship – Immunology (University of Nantes)

Postdoctoral Fellow – Foxp3+ T-Regulatory in Autoimmunity and Transplantation (Children’s Hospital of Philadelphia)

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