Immune Regulation News Volume 5.47 | Dec 6 2013

TIM-4 Glycoprotein-Mediated Degradation of Dying Tumor Cells by Autophagy Leads to Reduced Antigen Presentation and Increased Immune Tolerance
T cell immunoglobulin- and mucin domain-containing molecule-4 (TIM-4) was found to be highly expressed on tumor-associated myeloid cells such as macrophages and dendritic cells and danger-associated molecular patterns released from chemotherapy-damaged tumor cells induced TIM-4 on tumor-associated myeloid cells recruited from bone marrow-derived precursors. [Immunity] Abstract | Graphical Abstract

FoxP3 Acts as a Cotranscription Factor with STAT3 in Tumor-Induced Regulatory T Cells
The authors identified an interleukin-10 (IL-10)-producing FoxP3⁺ T regulatory cell population that contributes to IL-10-dependent type 2 cytokine bias in breast-cancer patients. [Immunity] Abstract

IL-2 Therapy Promotes Suppressive ICOS+ Treg Expansion in Melanoma Patients
Investigators evaluated Treg population subsets that were induced in patients with melanoma following high-dose IL-2 therapy. They identified a Treg population that was positive for CD4, CD25, Foxp3, and the inducible T cell costimulator (ICOS). [J Clin Invest] Full Article | Press Release

Natural Killer Cell NKG2D and Granzyme B Are Critical for Allergic Pulmonary Inflammation
Researchers investigated the importance of natural killer (NK) cells in house dust mite-triggered allergic pulmonary inflammation. Specifically, they aimed to determine the role of the major NK-cell activating receptor NKG2D and NK-cell effector functions mediated by granzyme B. [J Allergy Clin Immun]
Abstract | Press Release

Diacylglycerol Kinase ζ Limits the Generation of Natural Regulatory T Cells
The authors found that loss of diacylglycerol Kinase ζ resulted in increased numbers of thymic CD25⁺Foxp3^–CD4⁺ natural regulatory T (nT_reg) cell precursors and Foxp3⁺CD4⁺ nT_reg cells in a cell-autonomous manner. [Sci Signal] Abstract | Press Release

Antigen-Specific Expansion of Human Regulatory T Cells as a Major Tolerance Mechanism against Mucosal Fungi
Scientists used a sensitive enrichment technology for antigen-reactive T cells to directly compare the conventional vs. regulatory CD4⁺ T-cell response directed against two ubiquitous mucosal fungi, Aspergillus fumigatus and Candida albicans. [Mucosal Immunol] Abstract

Cross-Talk between Aryl Hydrocarbon Receptor and the Inflammatory Response: A Role for NF-κB
Results show for the first time that NF-κB RelA is a critical component regulating the expression of Aryl hydrocarbon receptor (AhR) and the induction of AhR-dependent gene expression in immune cells illustrating the interaction of AhR and NF-κB signaling. [J Biol Chem] Abstract | Full Article

B Cell Regulation of Anti-Tumor Immune Response
Ongoing experiments in the laboratory indicate that B cells migrate to the site of tumor and acquire expression of immunosuppressive ligands and/or cytokines that contribute to the inhibition of anti-tumor immune response. Significant infiltration of human tumors by Treg cells as well as B cells suggests that observations made in murine systems may be applicable to human tumors as well. [Immunol Res] Abstract

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Three Cancer Research Powerhouses Form Immunotherapy Startup
Fred Hutchinson Cancer Research Center is advancing its legacy in immunotherapy by means of a new Seattle biotechnology company that is a unique collaboration among scientists at the Hutch, Memorial Sloan-Kettering Cancer Center in New York and Seattle Children’s Research Institute. [Fred Hutchinson Cancer Research Center] Press Release

TxCell Obtains Manufacturing Accreditation Status for Its French Cell Therapy Manufacturing Facility
TxCell SA, a biotechnology company developing innovative, personalized cell-based immunotherapies using antigen-specific regulatory T-cells for chronic inflammatory and autoimmune diseases, announced that it received a Manufacturing Accreditation delivered by the French National Agency for Drug Safety. [TxCell SA] Press Release

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