Immune Regulation News Volume 5.25 | Jul 5 2013

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 T_FH 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 (T_FH) 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]
Abstract

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

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

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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

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European Medicines Agency (European Union)

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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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