期刊
EXPERT OPINION ON THERAPEUTIC TARGETS
卷 21, 期 2, 页码 191-200出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/14728222.2017.1275568
关键词
GARP; latent TGF-beta; T regulatory cells; foxp3; suppression; integrins
资金
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases
Introduction: Foxp3(+) T regulatory cells (Tregs) play critical roles in immune homeostasis primarily by suppressing many aspects of the immune response. Tregs uniquely express GARP on their cell surface and GARP functions as a delivery system for latent TGF-. As Treg-derived TGF- may mediate the suppressive functions of Tregs, GARP may represent a target to inhibit Treg suppression in cancer or augment suppression in autoimmunity.Areas covered: This article will focus on 1) the role of Treg-derived TGF- in the suppressive activity of Treg, 2) the cellular and molecular regulation of expression of GARP on mouse and human Tregs, 3) the role of integrins in the activation of latent-TGF-/GARP complex, 4) an overview of our present understanding of the function of the latent-TGF-/GARP complex.Expert opinion: Two approaches are outlined for targeting the L-TGF-1/GARP complex for therapeutic purposes. Tregs play a major role in suppressive effector T cell responses to tumors and TGF-1 may be a major contributor to this process. One approach is to specifically block the production of active TGF-1 from Tregs as an adjunct to tumor immunotherapy. The second approach in autoimmunity is to selectively enhance the production of TGF- by Tregs at sites of chronic inflammation.
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