Immune Regulation News Volume 6.27 | Jul 25 2014

Type-I Interferon Signaling Through ISGF3 Complex Is Required for Sustained Rip3 Activation and Necroptosis in Macrophages
Scientists evaluated the mechanisms that lead to the induction of necrotic cell death in macrophages. They demonstrate that IFN-β-induced necroptosis of macrophages proceeds through tonic IFN-stimulated gene factor 3 (ISGF3) signaling, which leads to persistent expression of STAT1, STAT2, and IFN-regulatory factor 9.
[Proc Natl Acad Sci USA] Abstract

The Development of Autoimmune Features in Aging Mice Is Closely Associated with Alterations of the Peripheral CD4⁺ T-Cell Compartment
Some signs of potential autoimmunity, such as the appearance of anti-nuclear antibodies become prevalent with age. Scientists investigated whether the same holds true for inbred strains of mice and report that a disturbed T-cell homeostasis may drive the onset of some autoimmune features. [Eur J Immunol] Abstract

Innate IFN-γ Promotes Development of Experimental Autoimmune Encephalomyelitis: A Role for NK Cells and M1 Macrophages
The role of IFN-γ in the pathogenesis of autoimmune diseases is controversial. Although Th1 cells can induce experimental autoimmune encephalomyelitis (EAE), IFN-γ can suppress Th17 cells that are pathogenic in EAE. Investigators show that NK cells provide an early source of IFN-γ during development of EAE. [Eur J Immunol] Abstract

Insulin-Like Growth Factor-1 Induces Regulatory T Cell-Mediated Suppression of Allergic Contact Dermatitis in Mice
Scientists demonstrate that ectopic expression of insulin-like growth factor-1 in mouse skin suppresses allergic contact dermatitis in a regulatory T (Treg) cell-specific manner, increasing the number of Foxp3⁺ Treg cells in the affected area and stimulating lymphocyte production of the anti-inflammatory cytokine interleukin 10.
[Dis Model Mech] Full Article

Members of the Novel UBASH3/STS/TULA Family of Cellular Regulators Suppress T-Cell-Driven Inflammatory Responses In Vivo
Investigators examined the immune responses in trinitrobenzene sulfonic acid-induced colitis in a mouse model of human inflammatory bowel disease, in which T cells have a crucial role in the development of a pathological inflammatory condition. [Immunol Cell Biol] Abstract

Specific Deletion of LDL Receptor-Related Protein on Macrophages Has Skewed In Vivo Effects on Cytokine Production by Invariant Natural Killer T Cells
Scientists investigated whether a structurally related receptor to the low density lipoprotein (LDL) receptor, known as LDL receptor-related protein (LRP), plays a role in invariant natural killer T (iNKT) cell activation. They also show that CD169⁺ macrophages (MΦs), known to present antigen to iNKT cells, exhibited increased expression of LRP compared to CD169^– MΦs. [PLoS One] Full Article

Soluble MHC-II Proteins Promote Suppressive Activity in CD4⁺ T-Cells
Scientists report evidence for the role of soluble MHC-II proteins in immune response suppression and maintenance of tolerance, revealing novel regulatory mechanisms for immune system manipulation. [Immunology] Abstract

HMGB1-Mediated Early Loss of Transplanted Islets Is Prevented by Anti-IL-6R Antibody in Mice
The effect of anti-interleukin-6 receptor (IL-6R) antibody on amelioration of hyperglycemia in streptozocin-induced diabetic mice receiving 200 islets into the liver from a single donor was evaluated in association with high-mobility group box 1 (HMBG1)-stimulated interferon-γ production of hepatic mononuclear cells. [Pancreas] Abstract

CASP Is Involved in Migration and IFN-γ Secretion in Natural Killer Cells
Cytohesin associated scaffolding protein (CASP) is a highly expressed lymphocyte adaptor protein that forms complexes with vesicles and sorting proteins including SNX27 and Cytohesin-1. Investigators show that by using stably integrated shRNA, CASP has a direct role in the secretion of IFN-γ, and NK cell motility and ability to kill tumor cells. [Biochem Biophys Res Commun] Abstract

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Origin and Functions of Tissue Macrophages
The authors define the tools used for identifying the complex origin of tissue macrophages and discuss the relative contributions of tissue niche versus ontological origin to the regulation of macrophage functions during steady state and inflammation. [Immunity] Abstract

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Inovio Pharmaceuticals HPV Immunotherapy Achieves Primary Efficacy Endpoint in Randomized Phase II Cervical Dysplasia Trial
Inovio Pharmaceuticals, Inc. announced successful results from its randomized, double-blind, placebo-controlled phase II trial of VGX-3100 in women with biopsy-proven cervical intraepithelial neoplasia 2/3 (CIN2/3) associated with human papillomavirus (HPV) types 16 or 18. [Inovio Pharmaceuticals, Inc.] Press Release

Bristol-Myers Squibb and Ono Pharmaceutical Co., Ltd. Announce Strategic Immuno-Oncology Collaboration in Japan, South Korea and Taiwan
Bristol-Myers Squibb Company and Ono Pharmaceutical Co., Ltd. have signed a strategic collaboration agreement to jointly develop and commercialize multiple immunotherapies as single agents and combination regimens to help address the unmet medical needs of patients with cancer in Japan, South Korea and Taiwan. [Bristol-Myers Squibb] Press Release

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