Immune Regulation News Volume 9.32 | Aug 25 2017

TOP STORY

Allergies? Exhausted Regulatory T Cells May Play a Role

Researchers have evidence that the specialized T cells responsible for maintaining a balanced immune response are vulnerable to exhaustion that disrupts normal functioning and may even contribute to allergic reactions. The report is believed to be the first to suggest that regulatory T cells are subject to the functional exhaustion that also plagues conventional T cells that fight infectious agents and tumor cells. [Press release from St. Jude Children’s Research Hospital discussing online prepublication in Nature] Press Release | Abstract

(Ranked by impact factor of the journal)

CMTM6 Maintains the Expression of PD-L1 and Regulates Anti-Tumor Immunity

Researchers identified the uncharacterized protein CMTM6 as a critical regulator of PD-L1 in a broad range of cancer cells, by using a genome-wide CRISPR–Cas9 screen. Using a quantitative approach to profile the entire plasma membrane proteome, they found that CMTM6 displayed specificity for PD-L1. Notably, CMTM6 depletion decreased PD-L1 without compromising cell surface expression of MHC class I. [Nature] Abstract | Press Release

Regulatory Innate Lymphoid Cells Control Innate Intestinal Inflammation

Scientists identified a regulatory subpopulation of innate lymphoid cells (called ILCregs) that exist in the gut and harbors a unique gene identity that is distinct from that of ILCs or Tregs. During inflammatory stimulation, ILCregs could be induced in the intestine and suppress the activation of ILC1s and ILC3s via secretion of IL-10, leading to protection against innate intestinal inflammation. [Cell] Abstract | Graphical Abstract

Treg Depletion Potentiates Checkpoint Inhibition in Claudin-Low Breast Cancer

The authors have shown that intrinsic and immune cell gene signatures distinguish the claudin-low subtype clinically as well as in mouse models of other breast cancer subtypes. Antitumor efficacy required stringent Treg depletion combined with checkpoint inhibition; delays in tumor growth were not observed using therapies that modestly diminished the number of Tregs in the tumor microenvironment. [J Clin Invest] Full Article | Press Release

Activated Protein C Protects from GvHD via PAR2/PAR3 Signaling in Regulatory T-Cells

Scientists showed that the protease-activated protein C (aPC), which is generated by thrombomodulin, ameliorates graft-vs.-host disease (GvHD) aPC restricts allogenic T-cell activation via the protease activated receptor (PAR)2/PAR3 heterodimer on Tregs. Preincubation of pan T-cells with aPC prior to transplantation increased the frequency of Tregs and protects from GvHD. [Nat Commun] Full Article

JunB Promotes Th17 Cell Identity and Restrains Alternative CD4⁺ T-Cell Programs during Inflammation

Investigators showed the activator protein-1 (AP-1) factor JunB is an essential regulator of T helper 17 (Th17) cell identity. JunB activated expression of Th17 lineage-specifying genes and coordinately repressed genes controlling Th1 and regulatory T-cell fate. JunB supported Th17 cell identity by regulating key AP-1 complex constituents. [Nat Commun] Full Article

Foxp3-Independent Mechanism by Which TGF-β Controls Peripheral T Cell Tolerance

Using a transgenic model of autoimmune diabetes, the authors showed that ablation of TGF-β receptor II in T cells, but not Foxp3 deficiency, resulted in early-onset diabetes with complete penetrance. The rampant autoimmune disease was associated with enhanced T cell priming and elevated T cell expression of the inflammatory cytokine GM-CSF, concomitant with pancreatic infiltration of inflammatory monocytes that triggered immunopathology. [Proc Natl Acad Sci USA] Abstract

Ectopic Expression of Self-Antigen Drives Regulatory T Cell Development and Not Deletion of Autoimmune T Cells

Researchers demonstrated that ectopic expression of insulin epitope B:9–23 (InsB_9–23) by thymic APCs is insufficient to induce deletion of high- or low-affinity InsB_9–23–reactive CD4⁺ T cells; however, they observed an increase in the proportion and number of thymic and peripheral Foxp3⁺ regulatory T cells. [J Immunol] Abstract

Regulatory T Cell Subsets in Patients with Medulloblastoma at Diagnosis and during Standard Irradiation and Chemotherapy (PBTC N-11)

The authors evaluated circulating levels of immunosuppressive Tregs and other lymphocyte subsets in patients with newly diagnosed medulloblastoma undergoing surgery compared to a control cohort of patients undergo craniectomy for correction of Chiari malformation and further determined the impact of standard irradiation and chemotherapy on this cell population. [Cancer Immunol Immunother] Abstract

Transcriptional Repressor Blimp1 Regulates Follicular Regulatory T Cells Homeostasis and Function

Investigators document the function for B lymphocyte-induced maturation protein 1 (Blimp1) in T_FR cells in vitro and in vivo. Data presented demonstrated that T_FR cells indirectly inhibit the activation and differentiation of B cells by negatively regulating T_FR cells, thus lowering the secretion of antibody. Lack of Blimp1 made the immune suppression function of T_FR cells impaired in vitro. [Immunology] Abstract

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Enhancing Human Regulatory T Cells In Vitro for Cell Therapy Applications

With a particular focus on Tregs, the authors survey the diverse strategies that are being employed to enhance the efficacy of cell therapy via in vitro manipulation of cells, and highlight some emerging technologies that may propel this endeavor in the future. [Immunol Lett] Abstract

Visit our reviews page to see a complete list of reviews in the immune regulation research field.

CPRIT Awards $13M for Prevention, Research, Recruitment

Researchers in the NCI-designated Dan L Duncan Comprehensive Cancer Center have received $13,107,956 from the Cancer Prevention and Research Institute of Texas (CPRIT) for six new grants focused on evidence-based cancer prevention services, the recruitment of an established investigator, individual investigator and early translational research and core facility support. [Baylor College of Medicine] Press Release

Grid Therapeutics Signs Exclusive License Agreement to Develop a Novel Immuno-Oncology Antibody

Grid Therapeutics, LLC. announced the execution of an exclusive license agreement with Duke University to develop the first human derived antibody as a targeted immunotherapy for cancer. [Grid Therapeutics, LLC. (Business Wire, Inc.)] Press Release

Biomedical Ph.D. Program at Major Research University Drops GRE Requirement for Admission

The University of Michigan’s biomedical sciences graduate program announced that it will no longer require GRE scores for its Ph.D. admissions. Following a review of the available evidence and a public discussion involving the program’s faculty, staff, and trainees, the exam’s ability to predict student performance seems “weak at best” while it significantly disadvantages women, minorities, and students from low socioeconomic backgrounds, writes Scott Barolo, director of the Program in Biomedical Sciences, in the announcement. [Science Careers] Editorial

Leaked Documents Expose Long-Standing Gender Tensions at Salk Institute

Senior female faculty at the Salk Institute for Biological Studies raise more than twice as much in National Institutes of Health funding for scientists working in their labs as their male counterparts, according to a 2016 internal report on “faculty issues” requested by leaders of the San Diego, California institution. Yet Salk leaders favored male scientists by granting them greater access to internal funds and other resources, the report implies, echoing gender discrimination lawsuits filed last month against the research center. [ScienceInsider] Editorial

A Bold Open-Access Push in Germany Could Change the Future of Academic Publishing

Over the past two years, more than 150 German libraries, universities, and research institutes have formed a united front trying to force academic publishers into a new way of doing business. Instead of buying subscriptions to specific journals, consortium members want to pay publishers an annual lump sum that covers publication costs of all papers whose first authors are at German institutions. Those papers would be freely available around the world; meanwhile, German institutions would receive access to all the publishers’ online content. [ScienceInsider] Editorial

NEW Cell-Weizmann Institute of Science Symposium: Next Gen Immunology
February 11-14, 2018
Rehovot, Israel

Visit our events page to see a complete list of events in the community.

NEW Postdoctoral Research Associate – Mega Proteins to Control T Cell Signaling (University of Oxford)

NEW Postdoctoral Training Fellows – Cell Death & Inflammation (Institute of Cancer Research)

Postdoctoral Fellowship – Immunology (University of Georgia)

Postdoctoral Research Fellows – Systems Immunology (University of Oslo)

Postdoctoral Scholar – Regulation of Immune Responses (University of Iowa)

Postdoctoral Fellowships – Immune Signaling and Metabolism (St. Jude Children’s Research Hospital)

Postdoctoral Position – Mucosal Immunology (Sainte-Justine Hospital Research Center)

Research Fellow Position – Immunology Research (ShanghaiTech University)

Mouse Scientist – T Cell-Based Therapy (Tessa Therapeutics Pte Ltd.)

Postdoctoral Researcher – Tumor Immunology and Cancer Immunotherapy (University of California, Los Angeles)

Postdoctoral Fellow – Allergy and Immunology (New York University Medical Center)

Postdoctoral Fellow – Neuroimmunology (Duke University)

Postdoctoral Research Fellow – Cancer Immunotherapy (Fred Hutchinson Cancer Research Center)

Principal Senior Scientist – Human Disease Immune Profiling/Precision Immunology (Sanofi)

Postdoctoral Fellow – Cell Biology and Innate Immunity (The Laboratory for Molecular Infection Medicine Sweden)

Assistant Associate or Full Member – Cancer Immunology (Fred Hutchinson Cancer Research Center)

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