Immune Regulation News Volume 9.10 | Mar 17 2017

TOP STORY

T Cells Control the Generation of Nanomolar-Affinity Anti-Glycan Antibodies

To produce the next generation of more efficacious conjugate vaccines, investigators explored a synthetic design aimed at focusing both B cell and T cell recognition to a single short glycan displayed at the surface of a virus-like particle. [J Clin Invest] Full Article

(Ranked by impact factor of the journal)

Circulating Gluten-Specific FOXP3⁺CD39⁺ Regulatory T Cells Have Impaired Suppressive Function in Celiac Disease

The authors defined if celiac disease patients have a dysfunction or lack of gluten-specific FOXP3⁺ Tregs. Treated celiac disease patients underwent oral wheat challenge to stimulate re-circulation of gluten-specific T-cells. [J Allergy Clin Immunol] Abstract

IL-21 Restricts T Follicular Regulatory T Cell Proliferation through Bcl-6 Mediated Inhibition of Responsiveness to IL-2

T follicular regulatory cells control the magnitude and specificity of the germinal centre reaction, but how regulation is contained to ensure generation of high-affinity antibody is unknown. Researchers showed that this balance is maintained by the reciprocal influence of interleukin (IL)-2 and IL-21. [Nat Commun] Full Article

ORAI2 Modulates Store-Operated Calcium Entry and T Cell-Mediated Immunity

Investigators showed that deletion of Orai1 reduces, whereas deletion of Orai2 increases, store-operated Ca²⁺ entry in mouse T cells. These distinct effects are due to the ability of ORAI2 to form heteromeric channels with ORAI1 and to attenuate Ca²⁺ release-activated Ca²⁺ channel function. [Nat Commun] Full Article

Eosinophil-Derived IL-4 Drives Progression of Myocarditis to Inflammatory Dilated Cardiomyopathy

Scientists used the experimental autoimmune myocarditis model to determine the role of eosinophils in myocarditis and inflammatory dilated cardiomyopathy (DCMi). Eosinophils were dispensable for myocarditis induction but were required for progression to DCMi. [J Exp Med] Abstract | Press Release

BET N-Terminal Bromodomain Inhibition Selectively Blocks Th17 Cell Differentiation and Ameliorates Colitis in Mice

The authors report that selective inhibition of the first bromodomain of bromodomain and extraterminal domain (BET) proteins with our newly designed small molecule MS402 inhibits primarily T-helper 17 (Th17) cell differentiation with a little or almost no effect on Th1 or Th2 and Treg cells. [Proc Natl Acad Sci USA] Abstract

Exhaustion-Associated Regulatory Regions in CD8⁺ Tumor-Infiltrating T Cells

Researchers investigated the relation between gene expression and chromatin accessibility in CD8⁺ tumor-infiltrating lymphocytes that recognize a model tumor antigen and have features of both activation and functional exhaustion. [Proc Natl Acad Sci USA] Abstract

The Autophagy Machinery Restrains iNKT Cell Activation through CD1D1 Internalization

Investigators report that mice with dendritic cell-specific deletion of the essential autophagy gene Atg5 showed better CD1D1-restricted glycolipid presentation in vivo. These effects led to enhanced invariant natural killer T (iNKT) cell cytokine production upon antigen recognition and lower bacterial loads during Sphingomonas paucimobilis infection. [Autophagy] Abstract

P2X7 Receptor Promotes Intestinal Inflammation in Chemically Induced Colitis and Triggers Death of Mucosal Regulatory T Cells

P2X7 receptor knockout induced regulatory T cell accumulation in the colon, as evaluated by qRT-PCR for FoxP3 expression and immunostaining for CD90/CD45RB^low. Flow cytometry analysis of mesenteric lymph node cells showed that P2X7 activation triggered regulatory T cell death. [Biochim Biophys Acta] Abstract

CD117⁺CD44⁺ Stem T Cells Develop in the Thymus and Potently Suppress T-Cell Proliferation by Modulating the CTLA-4 Pathway

Flow cytometry was used to analyze different populations of thymocytes, and T-cell proliferation assays, RT-PCR, and real-time RT-PCR were used to characterize the stem cells and examine the function of CD44⁺CD117⁺ cells. [Stem Cell Res Ther] Full Article

T Regulatory Cells Are Critical for the Maintenance, Anamnestic Expansion, and Protection Elicited by Vaccine-Induced CD8 T Cells

Scientists demonstrated that transient absence of T regulatory cells during effector to memory CD8 T cell transition results in a permanent impairment in the maintenance, function, and recall capacity of CD8 T cells. [Immunology] Abstract

Antitumor Activity of Orally Administered Maitake α-Glucan by Stimulating Antitumor Immune Response in Murine Tumor

The authors found that oral administration of YM-2A could inhibit tumor growth and improve survival rate in two distinct mouse models of colon-26 carcinoma and B16 melanoma. Orally administered YM-2A enhanced antitumor immune response by increasing INF-γ-expressing CD4⁺ and CD8⁺ cells in the spleen and INF-γ-expressing CD8⁺ cells in tumor-draining lymph nodes. [PLoS One] Full Article

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Dying Cells Actively Regulate Adaptive Immune Responses

The authors provide a detailed summary of both the passive and active signals that are generated by dying cells during their initiation of CD8⁺ T cell-mediated immunity. They propose that molecules generated alongside cell death pathways — inducible damage-associated molecular patterns — are upstream immunological cues that actively regulate adaptive immunity. [Nat Rev Immunol] Abstract

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

Vedantra Pharmaceuticals Announces a Joint Research Collaboration with Neon Therapeutics to Develop Cancer Vaccines

Vedantra Pharmaceuticals, Inc. announced a joint collaboration to explore cancer vaccine research with Neon Therapeutics. [Vedantra Pharmaceuticals, Inc.] Press Release

Stellar Biotechnologies and Matrivax Sign Agreement to Transfer Vaccine Technology

Stellar Biotechnologies, Inc. and Matrivax Inc. announced that the companies have entered into a technology transfer and purchase agreement related to Stellar’s proprietary Clostridium difficile technology. [Stellar Biotechnologies, Inc.] Press Release

United Kingdom Moves Forward with Controversial Embryo Technique

Making heritable genetic changes to eggs and sperm was prohibited in the United Kingdom until Parliament approved a new law allowing the technique in 2015. In December 2016, the Human Fertilization and Embryo Authority announced that it would be willing to grant a license to use the technique in patients. The Telegraph reported that the agency has granted its first license to Newcastle University, where researchers have been working on lab-based experiments for years. [ScienceInsider] Editorial

Pasteur Institute’s Scientists Make Last-Ditch Plea to Keep Their President

Following a string of failed attempts to keep their president Christian Bréchot on after he reaches the mandated retirement age, leading researchers have continued to agitate quietly in his favor — even though the institute’s board of directors has made what seems to be a final decision on the matter and is starting a search for Bréchot’s successor. [Nature News] Editorial

US Science Agencies Face Deep Cuts in Trump Budget

When it comes to science, there are few winners in US President Donald Trump’s first budget proposal. The plan outlines double-digit cuts for the Environmental Protection Agency and the National Institutes of Health. The Trump budget would cut funding for the entire NIH by 18%, to $25.9 billion, making it one of the hardest-hit research agencies. [Nature News] Editorial

NEW Keystone Symposium: Cell Death and Inflammation
May 29-June 2, 2017
Dublin, Ireland

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NEW Postdoctoral Research Fellowship – Tumor Immunology (University of Oslo)

Research Technologist – Cell Separation & Immunology (STEMCELL Technologies, Inc.)

Postdoctoral Position – Translational Immunology (German Cancer Research Center)

PhD Student Position – Mucosal Immunology (Karolinska Institutet)

Principal Scientist – Immuno Oncology (Celgene Corporation)

Postdoctoral Researcher – Development of Immune System (Lund University)

Research Investigator – Immuno-Oncology (Bristol-Meyers Squibb)

Associate/Full Professor – Immunobioengineering (University of Toronto)

Scientist – Immunology (Moderna Therapeutics)

Senior Scientist – (Immatics Biotechnologies GmbH)

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

Postdoctoral Fellow – Molecular Immunology (University of California, San Diego)

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