TGFbeta1 and Treg cells: alliance for tolerance.
Transforming 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.
Bommireddy
Ramireddy
R
BIO5 Institute, University of Arizona, PO Box 245217, Tucson, AZ 85724-5217, USA. ramiredb@email.arizona.edu
Doetschman
Thomas
T
D000818:Animals; D001327:Autoimmune Diseases / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D008954:Models, Biological; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*
D053773:Transforming Growth Factor beta1