5_signalling.pptVIP

ge.jin@/3683791 TGF-beta is prototypic protein of a family that are involved in cell growth, proliferation, differentiation, and apoptosis. The TGF-beta family consists of more than 30 members. TGF-beta 1-3 are particularly interesting as they are remarkably mutifunctional and indispensable. Knockout mouse animal models have shown that deficiency of any of the gene is lethal. TGFbeta1 is the most abundant form of TGF-beta and as such is often referred to as TGF-beta. It was originally identified for its ability to promote the growth of fibroblasts and assigned to chromosome 19 in humans and to chromosome 7 in mice. The human and mouse homologues differ by only one residue in their amino acid sequence. TGF-β1 is produced by every leukocyte lineage and has profound regulatory effects on a myriad of developmental, physiological and immune processes. In general, TGF-β1 possesses both pro- and anti-inflammatory activity depending on the presence of other growth factors and the activation or differentiation state of the target cell. For example, at a site of developing inflammation TGF-β1 can modulate the expression of adhesion molecules, act as a chemoattractant, and orchestrate the immune response by suppressing or activating leukocytes. This orchestration by TGF-β1 also applies to the Th cell subset paradigm. TGF-β1 can alter the production of, and response to, cytokines of both Th subsets and can therefore skew Th1 or Th2 immune responses as it sees fit depending on the composition of the inflammatory environment. In fact, TGF-β1 secretion is a hallmark of a new candidate regulatory T cell subset called Th3 that also secretes IL-4 and IL-10. With such widespread responsibilities, it is no surprise that TGF-β1 knockout mice exhibit immune dysregulation and succumb to a progressive wasting syndrome shortly after birth. This mortal phenotype is characterized by changes in lymphoid organ architecture, including both the shrinking of the thymus and the swelling of lymph no