Description: Transforming Growth Factor beta (TGF beta) is a pleiotropic cytokine which exists in five isoforms, known as TGF beta 1-5, with homologies of 70-80% and no homology to TGF alpha. TGF beta 1 is the most abundant isoform and is ubiquitously expressed, while other isoforms are expressed in a more restricted manner. TGF beta 1 is highly conserved, with 100% sequence homology between the human, simian, bovine, porcine, and chicken proteins and 99% homology between the human and murine proteins. It is highly expressed in platelets and also produced by macrophages, lymphocytes, endothelial cells, chondrocytes, and leukemic cells.
TGF beta 1 is synthesized as a long precursor polypeptide, which is cleaved to yield the mature protein and the Latency Associated Peptide (LAP). LAP and mature TGF beta 1 remain non-covalently associated through secretion, forming homodimers known as the Small Latent Complex (SLC). Secretion can be induced by steroids, retinoids, EGF, NGF, vitamin D3, and IL-1. The bioactivity of mature TGF beta 1 is dependent on its release from LAP by conformational changes and proteolytic processing. Its activities include inhibition of cell growth in epithelial cells, endothelial cells, fibroblasts, neurons, lymphoid cells, and other hematopoietic cell types. TGF beta 1 also inhibits the proliferation of T cells and NK cells, downregulates the activities of activated macrophages, and blocks the anti-tumor activity of IL-2 – bearing lymphokine-activated killer (LAK) cells. Recently, TGF beta 1 has been found to have a critical role in the development of regulatory T cells and act as a costimulatory factor for expression of Foxp3. Dendritic cells exposed to tumors have been reported to secrete TGF beta 1 and stimulate the differntiation of CD4+CD25+ Treg cells from peripheral CD4+CD25- progeny. TGF beta 1-induced regulatory T cells have been termed iTreg.