Immune Regulation News Volume 8.06 | Feb 19 2016

Transient Inhibition of ROR-γT Therapeutically Limits Intestinal Inflammation by Reducing T_H17 Cells and Preserving Group 3 Innate Lymphoid Cells
Scientists demonstrated that transient chemical inhibition of RAR-related orphan receptor-γt (ROR-γt) in mice selectively reduces cytokine production from T helper 17 (T_H17) but not innate lymphoid cells in the context of intestinal infection with Citrobacter rodentium, resulting in preserved innate immunity. [Nat Med]
Abstract | Press Release

CD45 Phosphatase Inhibits STAT3 Transcription Factor Activity in Myeloid Cells and Promotes Tumor-Associated Macrophage Differentiation
Scientists demonstrated that differentiation of tumor-associated macrophages in tumor site from monocytic precursors was controlled by downregulation of the activity of the transcription factor STAT3. Decreased STAT3 activity was caused by hypoxia and affected all myeloid cells but was not observed in tumor cells. [Immunity] Abstract | Graphical Abstract | Press Release

Glycogen Synthase Kinase 3 Inactivation Drives T-Bet-Mediated Downregulation of Co-Receptor PD-1 to Enhance CD8⁺ Cytolytic T Cell Responses
Researchers identified glycogen synthase kinase 3 (GSK-3) as a key upstream kinase that regulated PD-1 expression in CD8⁺ T cells. GSK-3 siRNA downregulation, or inhibition by small molecules, blocked PD-1 expression, resulting in increased CD8⁺ cytotoxic T lymphocyte function. [Immunity]
Full Article | Graphical Abstract

A Hematopoietic Cell–Driven Mechanism Involving SLAMF6 Receptor, SAP Adaptors and SHP-1 Phosphatase Regulates NK Cell Education
Activation of natural killer (NK) cells by hematopoietic target cells is controlled by the SLAM family of receptors and by the associated SAP family of adaptors. Investigators found that SLAM receptors also enhanced NK cell activation by nonhematopoietic target cells, which lack ligands for SLAM receptors. [Nat Immunol] Abstract

Voluntary Running Suppresses Tumor Growth through Epinephrine- and IL-6-Dependent NK Cell Mobilization and Redistribution
Tumor-bearing mice randomized to voluntary wheel running showed over 60% reduction in tumor incidence and growth across five different tumor models. Microarray analysis revealed training-induced upregulation of pathways associated with immune function. NK cell infiltration was significantly increased in tumors from running mice, whereas depletion of NK cells enhanced tumor growth and blunted the beneficial effects of exercise. [Cell Metab] Full Article | Graphical Abstract | Press Release

TGF-β Inhibits the Activation and Functions of NK Cells by Repressing the mTOR Pathway
Scientists provide genetic, pharmacologic, and biochemical evidence that a critical target of transforming growth factor–β (TGF-β) signaling in mouse and human natural killer (NK) cells is the serine and threonine kinase mTOR (mammalian target of rapamycin). [Sci Transl Med] Abstract

YY1 Inhibits Differentiation and Function of Regulatory T Cells by Blocking Foxp3 Expression and Activity
Researchers showed that YY1 expression is lower in regulatory T (T_reg) cells than T_conv cells, and its overexpression causes a marked reduction of Foxp3 expression and abrogation of suppressive function of T_reg cells. [Nat Commun] Full Article

Intralymphatic CCL21 Promotes Tissue Egress of Dendritic Cells through Afferent Lymphatic Vessels
The authors describe a role for the chemokine CCL21 in intralymphatic dendritic cell (DC) crawling. They found that blockade of CCL21—but not the absence of lymph flow—completely abolished DC migration from capillaries toward collecting vessels and reduced the ability of intralymphatic DCs to emigrate from skin. [Cell Rep] Full Article | Graphical Abstract | Press Release | Video

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Cancer MoonShot 2020 Announces the Formation of a National Pediatrics Consortium, a Major Milestone in the War on Cancer in Children
Cancer MoonShot 2020 announced another milestone in its quest to alter the course of cancer care with the formation of the Pediatrics Consortium focused on bringing the promise of combined immunotherapy as the next-generation standard of cancer care to children diagnosed with the disease. [Cancer MoonShot 2020] Press Release

Effimune, In Cell Art Launch Cancer Immunotherapy Collaboration
Effimune will use In Cell Art’s Nanotaxi^® technology to develop cancer immunotherapies based on producing antibodies from a patient’s body. The companies will compare the efficacy of that approach to traditional production of antibodies through a bioreactor during the 12-month collaboration. [Effimune (Genetic Engineering & Biotechnology News)] Press Release

AVROBIO Inc. Launches to Develop Novel, Clinical-Stage Cell and Gene Therapies Targeting Immuno-Oncology and Rare Diseases
AVROBIO announced its launch plans to accelerate development of two novel cell and gene therapies. Phase I programs will be in the clinic by early to mid-2016 in both acute myeloid leukemia and Fabry disease. [AVROBIO Inc.] Press Release

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