Volume 5.25 | Jul 5

Immune Regulation News 5.25 July 5, 2013
Pulmonary Cell News
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Maintaining Immune Balance Involves an Unconventional Mechanism of T Cell Regulation
Researchers showed that a molecular complex called mTORC1 uses an unconventional process to serve as a rheostat, controlling the supply and function of regulatory T cells. Loss of mTORC1 activity impairs the regulatory T cells that suppress the immune system’s inflammatory response. The mTORC1 complex is part of the mTOR pathway, which was thought to inhibit rather than promote the number and function of regulatory T cells. [Press release from St. Jude Children’s Research Hospital discussing online prepublication in Nature]
Press Release
| Abstract
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PUBLICATIONS (Ranked by impact factor of the journal)
The Microbial Metabolites, Short-Chain Fatty Acids, Regulate Colonic Treg Cell Homeostasis
Investigators determined that short chain fatty acids, gut microbiota-derived bacterial fermentation products, regulate the size and function of the colonic regulatory T cell (Treg) pool and protect against colitis in a Ffar2(GPR43)-dependent manner in mice. [Science] Abstract

CD36 Coordinates NLRP3 Inflammasome Activation by Facilitating Intracellular Nucleation of Soluble Ligands into Particulate Ligands in Sterile Inflammation
Scientists identified an endocytic pathway mediated by the pattern-recognition receptor CD36 that coordinated the intracellular conversion of those soluble ligands into crystals or fibrils, which resulted in lysosomal disruption and activation of the NLRP3 inflammasome. Consequently, macrophages that lacked CD36 failed to elicit interleukin 1β (IL-1β) production in response to those ligands, and targeting CD36 in atherosclerotic mice resulted in lower serum concentrations of IL-1β and accumulation of cholesterol crystals in plaques. [Nat Immunol] Abstract | Press Release

MicroRNAs of the miR-17~92 Family Are Critical Regulators of TFH Differentiation
The authors report that mice with T cell-specific deletion of the miR-17~92 family of microRNAs (miRNAs) had substantially compromised follicular helper T cells (TFH) differentiation, germinal-center formation and antibody responses and failed to control chronic viral infection. [Nat Immunol] Abstract

Thymosin β4-Sulfoxide Attenuates Inflammatory Cell Infiltration and Promotes Cardiac Wound Healing
The authors revealed that thymosin β4-sulfoxide lies downstream of hydrogen peroxide in the wounded fish and triggers depletion of inflammatory macrophages at the injury site. This function is conserved in the mouse and observed after cardiac injury, where it promotes wound healing and reduced scarring. In human T-cell/CD14+ monocyte co-cultures, thymosin β4-sulfoxide inhibits interferon-γ, and increases monocyte dispersal and cell death, likely by stimulating superoxide production. [Nat Commun] Abstract

Functional Characterization of Foxp3-Specific Spontaneous Immune Responses
Investigators identified and characterized spontaneous cytotoxic immune responses to transcription factor forkhead box P3 (Foxp3) expressing cells in peripheral blood of healthy volunteers and cancer patients. These immune responses were directed against a HLA-A2 restricted peptide epitope derived from Foxp3. [Leukemia]

Quorum Sensing Allows T Cells to Discriminate between Self and Nonself
To minimize autoreactivity, immature T cells that respond to self-peptides are deleted in the thymus by a process called negative selection. However, negative selection is imperfect, and autoreactive T cells exist in healthy individuals. To understand how autoimmunity is yet avoided, without loss of responsiveness to pathogens, researchers have developed a model of T-cell training and response. [Proc Natl Acad Sci USA] Abstract

Host Genetic Background Impacts Modulation of the TLR4 Pathway by RON in Tissue-Associated Macrophages
The authors showed that recepteur d’origine nantais (RON) exerts divergent control over toll-like receptor 4 (TLR4) activity in macrophages from different mouse genetic backgrounds. RON potently modulated the TLR4 response in macrophages from M2-prone FVB mice, as compared with M1-skewed C57Bl6 mice. [Immunol Cell Biol] Full Article

PepT1 Expressed in Immune Cells Has an Important Role in Promoting the Immune Response during Experimentally Induced Colitis
Scientists used PepT1-knockout mice to explore the role played by PepT1 in immune cells during dextran sodium sulfate-induced colitis. They found that PepT1 in immune cells regulates the secretion of proinflammatory cytokines triggered by bacteria and/or bacterial products, and thus has an important role in the induction of colitis. [Lab Invest] Abstract

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How Ex Vivo Models Drive Progress in HIV Research: Read the Research Profiles
The Role of Dendritic Cells in Autoimmunity
The authors discuss the proposed roles of dendritic cells (DCs) in immunological tolerance, the effect of the gain or loss of DCs on autoimmunity and DC-intrinsic molecular regulators that help to prevent the development of autoimmunity. They also review the emerging roles of DCs in several autoimmune diseases, including autoimmune myocarditis, multiple sclerosis, psoriasis, type 1 diabetes and systemic lupus erythematosus. [Nat Rev Immunol] Abstract

Immunotherapy with Gene-Modified T Cells: Limiting Side Effects Provides New Challenges
This review discusses factors that might contribute to toxic side effects of therapy with gene modified T cells, and outline potential strategies to retain anticancer activity while reducing unwanted side effects.[Gene Ther] Abstract

NLRP6 in Infection and Inflammation
NLRs play fundamental roles in host-defense and inflammatory disorders. NLRP6 is a newly characterized member of this family that inhibits NF-κB and MAP-kinase dependent immune signaling to hamper anti-microbial defense. Further, NLRP6 regulates intestinal inflammation by maintaining gut microbiota composition. In this review, the authors examine the recent studies and emphasize the key functions regulated by NLRP6. [Microbes Infect] Abstract

Visit our reviews page to see a complete list of reviews in the immune regulation field.
Immune-Boosting Colorectal Cancer Drug Shows Promise
Research findings confirm the biological action of the drug called MGN1703 and suggest it may be possible to identify which gastrointestinal cancer patients will benefit most from the treatment. MGN1703 is a small DNA molecule recognized by a receptor called toll-like receptor 9 that is expressed in certain immune system cells. The drug is designed to broadly activate all components of the innate immune system to stimulate the destruction of cancer cells. [Press release from European Society for Medical Oncology (ESMO) discussing research presented at the ESMO 15th World Congress on Gastrointestinal Cancer, Barcelona] Press Release

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Transgene Grants Ascend Biopharmaceuticals a License to TG1042, an Immunotherapy to Treat Basal Cell Carcinoma, a Common Type of Skin Cancer
Transgene SA announced it is granting Ascend Biopharmaceuticals, an emerging privately-held Australian immunotherapy company, a license to develop and commercialize TG1042 in basal cell carcinoma, a highly prevalent form of skin cancer, as well as in two other cancer indications. TG1042 is an adenovirus- based immunotherapy that expects to enter phase I/II clinical trial in nodular basal cell carcinoma in Australia later in 2013. [Transgene SA] Press Release

Cancer Immunotherapy of Activision Artis Receives Orphan Drug Designation from U.S. Food and Drug Administration FD
Activision Artis has recently received orphan drug designation from the U.S. Food and Drug Administration for its innovative cancer immunotherapy AV0113. Specifically, the orphan drug designation refers to the application of Activision Artis’ AV0113-drug for the treatment of malignant glioma, the most aggressive of all brain tumors. [Activision Artis Biotech] Press Release

Anthera Announces Initiation of BRIGHT-SC Phase II Clinical Study in IgA Nephropathy with Blisibimod
Anthera Pharmaceuticals, Inc. announced it has initiated the BRIGHT-SC Phase II study of blisibimod, a novel inhibitor of B-Cell Activating Factor for the treatment of IgA nephropathy. [Anthera Pharmaceuticals, Inc.] Press Release
National Institutes of Health (United States)

Food and Drug Administration (United States)

Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)
NEW 46th Annual Meeting of the Society for Leukocyte Biology: Regulators of Innate Cell Plasticity
October 20-22, 2013
Newport, United States

Visit our events page to see a complete list of events in the immune regulation community.
NEW PhD Position – Cellular Signaling in the Immune System (Helmholtz Centre for Environmental Research – UFZ – Helmholtz Association)

NEW PhD Position – MMP-9 Domain Structure Involvement in Immunomodulation (KU Leuven)

PhD Research Position – Molecular and Cellular Mechanisms of Immune Tolerance and Autoimmunity (Weizmann Institute of Science)

Postdoctoral Position – Complement System in Acute and Chronic Inflammatory Diseases (Institute for Systemic Inflammation Research, University of Lübeck)

Postdoctoral Fellowship – Immune Regulation by Extracellular Matrix Proteins (Johns Hopkins University – School of Medicine)

Postdoctoral Scientists – Immune Cell Biology (Medical Research Council – National Institute for Medical Research)

Director of Cell Processing Facility (S L Collins Associates, Inc.)

Junior or Senior Group Leader – Immunology/Infection/Inflammation (Center of Pathophysiology of Toulouse Purpan)

Postdoctoral Position – Mechanistic Studies in Immune Responses (Medical University of Vienna)

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