Immune Regulation News Volume 7.00 | Jan 9 2015

T_reg Cells Require the Phosphatase PTEN to Restrain T_H1 and T_FH Cell Responses
Investigators found that the phosphatase PTEN links regulatory T cells (T_reg cells) cell stability to repression of type 1 helper T cell (T_H1 cell) and follicular helper T cell (T_FH cell) responses. Depletion of PTEN in T_reg cells resulted in excessive T_FH cell and germinal center responses and spontaneous inflammatory disease. [Nat Immunol] Abstract

Sterol Metabolism Controls T_H17 Differentiation by Generating Endogenous ​RORγ Agonists
Scientists report that during T_H17 differentiation, ​cholesterol biosynthesis and uptake programs are induced, whereas their metabolism and efflux programs are suppressed. These changes result in the accumulation of the cholesterol precursor, ​desmosterol, which functions as a potent endogenous ​retinoic acid receptor-related orphan receptor γ (​RORγt) agonist. [Nat Chem Biol] Abstract | Press Release

Proinflammatory TLR Signaling Is Regulated by a ​TRAF2-Dependent Proteolysis Mechanism in Macrophages
Researchers show that myeloid cell-specific ablation of ​TRAF2 greatly promotes toll-like receptor (TLR)-stimulated proinflammatory cytokine expression in macrophages and exacerbates colitis in an animal model of inflammatory bowel disease. [Nat Commun] Abstract

Intracellular Osteopontin Regulates Homeostasis and Function of Natural Killer Cells
Scientists report that deficient expression of intracellular osteopontin by natural killer (NK) cells results in defective responses to IL-15 associated with a substantial increase in the NK cell contraction phase of homeostatic expansion, defective expression of the Eomes transcription factor, and diminished responses to metastatic tumors. [Proc Natl Acad Sci USA] Abstract

miR-155 Augments CD8⁺ T-Cell Antitumor Activity in Lymphoreplete Hosts by Enhancing Responsiveness to Homeostatic γ_c Cytokines
Researchers found that microRNA-155 (miR-155) enabled tumor-specific CD8⁺ T cells to mediate profound antitumor responses in lymphoreplete hosts that were not potentiated by immune-ablation. miR-155 enhanced T-cell responsiveness to limited amounts of homeostatic γ_c cytokines, resulting in delayed cellular contraction and sustained cytokine production. [Proc Natl Acad Sci USA] Abstract

Syk Is Indispensable for CpG-Induced Activation and Differentiation of Human B Cells
Investigators describe a so far unidentified spleen tyrosine kinase (Syk)-dependent pathway which is indispensable for CpG-induced human B cell activation. They show that triggering of B cells by CpG results in Syk and src kinase phosphorylation, proliferation, as well as cytokine and antibody production independent of the BCR. [Cell Mol Life Sci] Abstract

Effector T Cells Boost Regulatory T Cell Expansion by IL-2, TNF, OX40, and Plasmacytoid Dendritic Cells Depending on the Immune Context
Activated effector CD4⁺ T cells can boost regulatory T (Treg) cell expansion through TNF or IL-2. Researchers further characterized this effector T cell-dependent Treg cell boost in vivo in mice. [J Immunol] Abstract

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Isis Pharmaceuticals Announces Collaboration with Janssen to Discover and Develop RNA-Targeted Therapeutics for Autoimmune Diseases in the GI Tract
Isis Pharmaceuticals, Inc. announced that the company has entered into a global collaboration with Janssen Biotech, Inc. to discover and develop antisense drugs to treat autoimmune disorders of the gastrointestinal (GI) tract. [Isis Pharmaceuticals, Inc.] Press Release

Sipuleucel-T in Prostate Cancer: Added Benefit Is Not Proven
The German Institute for Quality and Efficiency in Health Care examined in a dossier assessment whether Sipuleucel-T (Provenge) offers patients an added benefit over one of the appropriate comparator therapies. [Institute for Quality and Efficiency in Health Care] Press Release

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