| First Author | Ramaswamy M | Year | 2007 |
| Journal | J Immunol | Volume | 179 |
| Issue | 10 | Pages | 6384-8 |
| PubMed ID | 17982024 | Mgi Jnum | J:153874 |
| Mgi Id | MGI:4366431 | Doi | 10.4049/jimmunol.179.10.6384 |
| Citation | Ramaswamy M, et al. (2007) Cutting edge: Rac GTPases sensitize activated T cells to die via Fas. J Immunol 179(10):6384-8 |
| abstractText | In activated CD4(+) T cells, TCR restimulation triggers apoptosis that depends on interactions between the death receptor Fas and its ligand, FasL. This process, termed restimulation-induced cell death (RICD), is a mechanism of peripheral immune tolerance. TCR signaling sensitizes activated T cells to Fas-mediated apoptosis, but what pathways mediate this process are not known. In this study we identify the Rho GTPases Rac1 and Rac2 as essential components in restimulation-induced cell death. RNA interference-mediated knockdown of Rac GTPases greatly reduced Fas-dependent, TCR-induced apoptosis. The ability of Rac1 to sensitize T cells to Fas-induced apoptosis correlated with Rac-mediated cytoskeletal reorganization, dephosphorylation of the ERM (ezrin/radixin/moesin) family of cytoskeletal linker proteins, and the translocation of Fas to lipid raft microdomains. In primary activated CD4(+) T cells, Rac1 and Rac2 were independently required for maximal TCR-induced apoptosis. Activating Rac signaling may be a novel way to sensitize chronically stimulated lymphocytes to Fas-induced apoptosis, an important goal in the treatment of autoimmune diseases. |
