Immune Regulation News Volume 7.14 | Apr 24 2015

The Transcription Factor Lymphoid Enhancer Factor 1 Controls Invariant Natural Killer T Cell Expansion and Th2-Type Effector Differentiation
Researchers demonstrated a unique function for the transcription factor lymphoid enhancer factor 1 in the postselection expansion of invariant natural killer T cells through a direct induction of the CD127 component of the receptor for interleukin-7 and the transcription factor c-myc. [J Exp Med] Abstract

mir-17-92 Regulates Bone Marrow Homing of Plasma Cells and Production of Immunoglobulin G2c
Scientists ablated mir-17-92 in mature B cells and demonstrated that mir-17-92 is dispensable for conventional B-cell development in the periphery. mir-17-92-deficiency in B cells led to enhanced homing of plasma cells to the bone marrow during T-cell-dependent immune response and selectively impaired immunoglobulin G2c production. [Nat Commun] Abstract

NK Cells Require IL-28R for Optimal In Vivo Activity
IL-28R-deficient mice were more susceptible to growth of the natural killer (NK) cell-sensitive lymphoma. Specific loss of IL-28R in NK cells transferred into lymphocyte-deficient mice resulted in reduced LPS-induced IFN-γ levels and enhanced tumor metastasis. [Proc Natl Acad Sci USA] Abstract

Genetic Regulation of Fate Decisions in Therapeutic T Cells to Enhance Tumor Protection and Memory Formation
Investigators directly compared the impact of effector versus memory differentiation of therapeutic T cells in tumor-bearing mice by introducing molecular switches that regulate cell fate decisions via mTOR. Ectopic expression of RAS homologue enriched in the brain increased mTOR complex 1 signaling, promoted a switch to aerobic glycolysis and increased expansion of effector T cells. [Cancer Res] Abstract | Full Article

Intratumoral Myeloid Cells Regulate Responsiveness and Resistance to Antiangiogenic Therapy
Investigators found that the efficacy of angiogenic inhibitors targeting the VEGF/VEGFR pathway was dependent on induction of the angiostatic and immune-stimulatory chemokine CXCL14 in mouse models of pancreatic neuroendocrine and mammary tumors. Tumors reinitiated angiogenesis and immune suppression by activating PI3K signaling in all CD11b⁺ cells, rendering tumors nonresponsive to VEGF/VEGFR inhibition. [Cell Rep] Full Article | Graphical Abstract

Astrocyte-Derived TGF-β1 Accelerates Disease Progression in ALS Mice by Interfering with the Neuroprotective Functions of Microglia and T Cells
Scientists identified transforming growth factor-β1 (TGF-β1) as a negative regulator of neuroprotective inflammatory response. They demonstrated that astrocyte-specific overproduction of TGF-β1 in SOD1G93A mice accelerated disease progression in a non-cell-autonomous manner, with reduced IGF-I production in deactivated microglia and fewer T cells with an IFN-γ-dominant milieu. [Cell Rep]
Full Article | Graphical Abstract

B Cell Antigen Presentation Is Sufficient to Drive Neuroinflammation in an Animal Model of Multiple Sclerosis
Researchers found that B cells cooperated with dendritic cells to enhance experimental autoimmune encephalomyelitis (EAE) severity resulting from myelin oligodendrocyte glycoprotein (MOG) immunization. Increasing the precursor frequency of MOG-specific B cells, but not the addition of soluble MOG-specific Ab, is sufficient to drive EAE in mice expressing MHCII by B cells alone. [J Immunol] Abstract

Survival and Maintenance of Regulatory T Cells Require the Kinase TAK1
Investigators showed that regulatory T (Treg)-conditional ablation of the kinase TAK1 reduced the number of Treg cells in the peripheral lymphoid organs, causing abnormal activation of conventional T cells and autoimmune symptoms. Using an inducible gene knockout approach, they further demonstrated that TAK1 is crucial for the survival of Treg cells. [Cell Mol Immunol] Abstract

Involvement of RORγT-Overexpressing T Cells in the Development of Autoimmune Arthritis in Mice
Researchers determined the role of transcription retinoid-related orphan receptor gamma t (RORγt) expression in T cells on the development of collagen-induced arthritis (CIA). Methods CIA was induced in C57BL/6 and T cell-specific RORγt transgenic mice. [Arthritis Res Ther] Abstract | Full Article

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Inflammation-Cancer Feedback Loop Discovery Is a Step Toward Better Cancer Drugs
New findings hidden within the complex machinery behind the vicious cycle of chronic inflammation and cancer were presented by the University of Pittsburgh Cancer Institute. [Press release from the University of Pittsburgh discussing research presented at the 2015 American Association for Cancer Research (AACR) Annual Meeting, Philadelphia] Press Release

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Effimune Obtains Regulatory Approval for Phase I Clinical Trial in Humans of Its New Immunomodulator FR104
Effimune announced that it had received the authorization for a Phase I clinical trial of FR104, its drug candidate for controlling the regulation of the immune system. [Effimune] Press Release

Pfizer and Provectus Biopharmaceuticals Receive Patent Allowance for Use of PV-10 in Combination with Systemic Immunotherapy Agents in Treatment of Cancer
Provectus Biopharmaceuticals, Inc. announced that it has received from the US Patent and Trademark Office a Notice of Allowance for a joint patent application made with Pfizer, Inc. The patent will protect use of PV-10 in combination with certain other types of drugs in the treatment of melanoma and cancers of the liver. [Provectus Biopharmaceuticals, Inc.] Press Release

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NEW Postdoctoral Position – Immunology-Vaccinology (Université de Liège)

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