Immune Regulation News Volume 7.44 | Nov 20 2015

Pulmonary Epithelial Cell-Derived Cytokine TGF-β1 Is a Critical Cofactor for Enhanced Innate Lymphoid Cell Function
Scientists demonstrated that epithelial cell-derived cytokine TGF-β had a central role in the generation of the pulmonary immune response. Mice that specifically lacked epithelial cell-derived TGF-β1 displayed a reduction in type 2 innate lymphoid cells, resulting in suppression of interleukin-13 and hallmark features of the allergic response including airway hyperreactivity. [Immunity] Full Article | Graphical Abstract

DNAM-1 Controls NK Cell Activation via an ITT-Like Motif
The mechanism by which DNAM-1 controls natural killer (NK) cell–mediated cytotoxicity and cytokine production was elucidated. Cytotoxicity and cytokine production triggered by DNAM-1 were mediated via a conserved tyrosine- and asparagine-based motif in the cytoplasmic domain of DNAM-1. [J Exp Med] Abstract

Imbalanced Signal Transduction in Regulatory T Cells Expressing the Transcription Factor FoxP3
Investigators found that FoxP3⁺ T regulatory (Treg) cells have a broadly dampened activation of several pathways and signaling nodes upon TCR-mediated activation, with low phosphorylation of CD3ζ, SLP76, Erk1/2, AKT, or S6 and lower calcium flux. [Proc Natl Acad Sci USA] Abstract

Murine Germinal Center B Cells Require Functional Fms-Like Tyrosine Kinase 3 Signaling for IgG1 Class-Switch Recombination
The authors describe a role for fms-like tyrosine kinase 3 receptor (Flt3) during B-cell activation and antibody production. They showed that Flt3 is reexpressed on activated germinal center B cells and that lack of functional Flt3 signaling in peripheral B cells results in a specific deficiency in production of the antibody subclass IgG1. [Proc Natl Acad Sci USA] Abstract

Inhibition of A20 Expression in Tumor Microenvironment Exerts Anti-Tumor Effect through Inducing Myeloid-Derived Suppressor Cells Apoptosis
The treatment of tumor-bearing mice with small interfering RNA targeting A20 (si-A20) inhibited the growth of tumors. The infiltration of myeloid-derived suppressor cells was dramatically reduced after si-A20 treatment, as compared to control groups, whereas the numbers of dendritic cells and macrophages were not affected. [Sci Rep] Full Article

Adipose Tissue Macrophages Induce PPARγ-High FOXP3⁺ Regulatory T Cells
The authors revealed the contribution of adipose tissue macrophages (ATMs) to the induction and proliferation of adipose regulatory T cells (Tregs). ATMs isolated from mice under steady state conditions induced Tregs with high expression of PPARγ compared with splenic dendritic cells in vitro. [Sci Rep] Full Article

γδ T Cell–Dependent Regulatory T Cells Prevent the Development of Autoimmune Keratitis
Scientists showed that CD8⁺ αβ T cells are the drivers of autoimmune keratitis, because adoptive transfer of CD8⁺, but not CD4⁺, T cells to keratitis-resistant B10.TCRβ/δ^−/− hosts induced a high incidence of keratitis. [J Immunol] Abstract

Indirubin Increases CD4⁺CD25⁺Foxp3⁺ Regulatory T Cells to Prevent Immune Thrombocytopenia in Mice
Researchers aimed to investigate the effects of indirubin on CD4⁺CD25⁺Foxp3⁺ regulatory T (Treg) cells in immune thrombocytopenia CBA mice. Consistently, indirubin significantly enhanced the percentage and cell number of CD4⁺CD25⁺Foxp3⁺Treg cells in the peripheral blood, spleen and lymph nodes. [PLoS One] Full Article

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Manipulating Regulatory T Cells: A Promising Strategy to Treat Autoimmunity
Investigators summarize studies that demonstrate regression of autoimmune diseases using CD4⁺CD25⁺Foxp3⁺ regulatory T (Treg) cells as therapeutics. They also discuss approaches to generate polyclonal and autoantigen-specific Treg cells in vitro and in vivo. [Immunotherapy] Abstract

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Ludwig Cancer Research and Cancer Research Institute Partner with Targovax to Test Candidate Virotherapy in Early-Phase Clinical Trials
Ludwig Cancer Research and the Cancer Research Institute announced an agreement with the biotechnology company Targovax to evaluate its experimental virotherapy, ONCOS-102, in early phase clinical trials testing the virotherapy in combination with other, potentially synergistic immunotherapies such as checkpoint inhibitors. [Ludwig Cancer Research] Press Release

Merck KGaA, Darmstadt, Germany, and Pfizer Receive FDA Breakthrough Therapy Designation for Avelumab in Metastatic Merkel Cell Carcinoma
Merck KGaA and Pfizer announced that the US Food and Drug Administration (FDA) has granted avelumab, an investigational fully human antiPD-L1 IgG1 monoclonal antibody, Breakthrough Therapy designation for the treatment of patients with metastatic Merkel cell carcinoma who have progressed after at least one previous chemotherapy regimen. [Pfizer Inc.] Press Release

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)

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Senior Scientist – Immunology and Cell Separation (STEMCELL Technologies Inc.)

Staff Scientist – Immunology (Benaroya Research Institute at Virginia Mason)

Scientist – Preclinical Immunology (Kanyos Bio)

Senior Research Fellow – Cancer Biology/Immunology (Plymouth University)

Postdoctoral Fellow – Regulatory Functions of Immune-Checkpoint Proteins (Medical College of Wisconsin)

Postdoctoral Fellow – Metastatic Breast Cancer (Purdue University Center for Cancer Research)

Postdoctoral Fellow – Cancer Biology (The University of Texas MD Anderson Cancer Center)

Professor – Immunology (La Jolla Institute for Allergy & Immunology)

Scientist Position – Role of Inflammation and the Immune System in the Context of Tissue Regeneration (KU Leuven)

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