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TGFbeta1 and Treg cells: alliance for tolerance Bommireddy R; Doetschman TTrends Mol Med 2007[Nov]; 13 (11): 492-501Transforming growth factor beta1 (TGFbeta1), an important pleiotropic, immunoregulatory cytokine, uses distinct signaling mechanisms in lymphocytes to affect T-cell homeostasis, regulatory T (Treg)-cell and effector-cell function and tumorigenesis. Defects in TGFbeta1 expression or its signaling in T cells correlate with the onset of several autoimmune diseases. TGFbeta1 prevents abnormal T-cell activation through the modulation of Ca2+-calcineurin signaling in a Caenorhabditis elegans Sma and Drosophila Mad proteins (SMAD)3 and SMAD4-independent manner; however, in Treg cells, its effects are mediated, at least in part, through SMAD signaling. TGFbeta1 also acts as a pro-inflammatory cytokine and induces interleukin (IL)-17-producing pathogenic T-helper cells (Th IL-17 cells) synergistically during an inflammatory response in which IL-6 is produced. Here, we will review TGFbeta1 and its signaling in T cells with an emphasis on the regulatory arm of immune tolerance.|Animals[MESH]|Autoimmune Diseases/metabolism/physiopathology[MESH]|Humans[MESH]|Models, Biological[MESH]|Signal Transduction/genetics/physiology[MESH]|T-Lymphocytes, Regulatory/*metabolism[MESH]|Transforming Growth Factor beta1/genetics/*metabolism[MESH] |
