REGULATION OF IMMUNE-RESPONSES BY TGF-BETA

Citation
Jj. Letterio et Ab. Roberts, REGULATION OF IMMUNE-RESPONSES BY TGF-BETA, Annual review of immunology, 16, 1998, pp. 137-161
Citations number
132
Categorie Soggetti
Immunology
Journal title
ISSN journal
07320582
Volume
16
Year of publication
1998
Pages
137 - 161
Database
ISI
SICI code
0732-0582(1998)16:<137:ROIBT>2.0.ZU;2-G
Abstract
The transforming growth factor beta (TGF-beta) family of proteins are a set of pleiotropic secreted signaling molecules with unique and pote nt immunoregulatory properties. TGF-beta 1 is produced by every leukoc yte lineage, including lymphocytes, macrophages, and dendritic cells, and its expression serves in both autocrine and paracrine modes to con trol the differentiation, proliferation, and state of activation of th ese immune cells. TGF-beta can modulate expression of adhesion molecul es, provide a chemotactic gradient for leukocytes and other cells part icipating in an inflammatory response, and inhibit them once they have become activated. Increased production and activation of latent TGF-b eta have been linked to immune defects associated with malignancy and autoimmune disorders, to susceptibility to opportunistic infection, an d to the fibrotic complications associated with chronic inflammatory c onditions. In addition to these roles in disease pathogenesis, TGF-bet a is now established as a principal mediator of oral tolerance and can be recognized as the sine qua non of a unique subset of effector cell s that are induced in this process. The accumulated knowledge gained t hrough extensive in vitro functional analyses and from in vivo animal models, including newly established TGF-beta gene knockout and transge nic mice, supports the concept that clinical therapies based on modula tion of this cytokine represent an important new approach to the treat ment of disorders of immune function.