Maurya, Neeraj and Gujar, Ravindra and Gupta, Mamta and Yadav, Vinod and Verma, Saurabh and Sen, Pradip (2014) Immunoregulation of dendritic cells by the receptor T cell Ig and mucin protein-3 via Bruton's tyrosine kinase and c-Src. Journal of immunology (Baltimore, Md. : 1950), 193 (7). pp. 3417-25. ISSN 1550-6606
Full text not available from this repository. (Request a copy)Abstract
The receptor T cell Ig and mucin protein-3 (TIM-3) has emerged as an important regulator of innate immune responses. However, whether TIM-3-induced signaling promotes or inhibits the activation and maturation of dendritic cells (DCs) still remains uncertain. In addition, the TIM-3 signaling events involved in this immunoregulatory function are yet to be established. In this article, we report that TIM-3 crosslinking by anti-TIM-3 Ab inhibited DC activation and maturation by blocking the NF-κB pathway. After Ab-mediated crosslinking, TIM-3 became tyrosine phosphorylated, which then sequentially bound and activated the nonreceptor tyrosine kinases Bruton's tyrosine kinase (Btk) and c-Src. Activation of Btk-c-Src signaling in turn triggered the secretion of some inhibitory factor (or factors) from DCs that inhibited the NF-κB pathway and subsequent activation and maturation of DCs. Silencing of Btk or c-Src abrogated the inhibitory effects of TIM-3 on DCs. These results demonstrate an essential role for Btk-c-Src signaling in TIM-3-induced DC suppression. Thus, in addition to demonstrating an inhibitory role for TIM-3 signaling in DC activation, we define the molecular mechanism by which TIM-3 mediates this effect.
| Item Type: | Article |
|---|---|
| Depositing User: | Dr. K.P.S.Sengar |
| Date Deposited: | 09 Feb 2015 04:38 |
| Last Modified: | 09 Feb 2015 04:38 |
| URI: | http://crdd.osdd.net/open/id/eprint/1541 |
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