Immune Regulation News Volume 7.48 | Dec 18 2015

T-Box Transcription Factors Combine with the Cytokines TGF-β and IL-15 to Control Tissue-Resident Memory T Cell Fate
Researchers showed that CD8⁺CD103⁺ tissue-resident memory T cells, independent of circulating memory T cells, were sufficient for protection against infection and described molecular elements that were crucial for their development in skin and lung. [Immunity] Abstract

Oligodendrocyte Death Results in Immune-Mediated CNS Demyelination
To investigate whether oligodendrocyte death could cause this autoimmune response, investigators examined the oligodendrocyte ablation Plp1-CreER^T;ROSA26-eGFP-DTA mouse model. Late-onset disease was associated with increased numbers of T lymphocytes in the CNS and myelin oligodendrocyte glycoprotein-specific T cells in lymphoid organs. [Nat Neurosci] Abstract | Press Release

AKAP9 Regulates Activation-Induced Retention of T Lymphocytes at Sites of Inflammation
Researchers generated mice with a T cell-specific deletion of the scaffold protein A kinase anchoring protein 9 (AKAP9) and use models of inflammatory disease to demonstrate that AKAP9 is dispensable for T cell priming and migration into tissues and lymph nodes, but is required for T cell retention in tissues. [Nat Commun] Full Article

T Cell Intrinsic USP15 Deficiency Promotes Excessive IFN-γ Production and an Immunosuppressive Tumor Microenvironment in MCA-Induced Fibrosarcoma
Investigators found that the USP15-deficient mice are hypersensitive to methylcholantrene (MCA)-induced fibrosarcomas. Excessive IFN-γ production in USP15-deficient mice promotes expression of the immunosuppressive molecule PD-L1 and the chemokine CXCL12, causing accumulation of T-bet⁺ regulatory T cells and CD11b⁺Gr-1⁺ myeloid-derived suppressor cells at tumor site. [Cell Rep]
Full Article | Graphical Abstract

Transpresentation of Interleukin-15 by IL-15/IL-15Rα mRNA-Engineered Human Dendritic Cells Boosts Antitumoral Natural Killer Cell Activity
Investigators engineered monocyte-derived dendritic cells to produce interleukin (IL)-15 and/or IL-15 receptor alpha (IL-15Rα) using mRNA electroporation. The addition of IL-15Rα to the protocol, enabling IL-15 transpresentation to neighboring natural killer (NK) cells, resulted in significantly better NK-cell activation compared to IL-15 alone. [Oncotarget] Full Article

Suppression of Established Hepatocarcinoma in Adjuvant Only Immunotherapy: Alum Triggers Anti-Tumor CD8⁺ T Cell Response
The authors report that injection of alum, the most widely used human adjuvant, into mice carrying H22 hepatocarcinoma resulted in a significant reduction of tumor growth with extended animal survival. This effect was associated with an increased specific CD8⁺ T cell activation and an inflammatory environment, yet with minimal overt side effects. [Sci Rep] Full Article

Accumulation Mechanisms of CD4⁺CD25⁺FOXP3⁺ Regulatory T Cells in EBV-Associated Gastric Carcinoma
Because regulatory T cells (Tregs) are regarded as a critical hurdle in anti-tumour immunity, the authors assessed the distribution of Tregs in 45 cases of Epstein-Barr virus (EBV)-associated gastric carcinomas (EBVaGCs) and 45 cases of EBV-negative gastric carcinoma (EBVnGC) with matched clinicopathological parameters by immunohistochemistry. They showed that Tregs were significantly increased in EBVaGC compared to EBVnGC. [Sci Rep] Full Article

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Treatment of Lupus : Lupuzor™ Enters Phase III
Lupuzor™ may become the first specific and non-immunosuppressant therapy for lupus, a disabling autoimmune disease that is currently incurable. This peptide is the subject of a CNRS patent and has already successfully completed Phases I and II of its regulatory clinical trials. [CNRS] Press Release

Neovacs Signs a Strategic Partnering Agreement with the Korean Company CKD Pharmaceutical Corp.
NEOVACS announced the signature of an exclusive licensing agreement with Chong Kun Dang (CKD) Pharmaceutical Corp. to market the IFNα-Kinoïd for the indications of lupus and dermatomyositis, in South Korea. [Neovacs SA] Press Release

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