Cutting edge: Rac GTPases sensitize activated T Cells to die via Fas
Cutting edge: Rac GTPases sensitize activated T Cells to die via Fas
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DOI：
10.4049/jimmunol.179.10.6384
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发表时间：
2007-11-15
影响因子：
4.4
通讯作者：
Siegel, Richard M.
中科院分区：
文献类型：
--
作者：
Ramaswamy, Madhu;Dumont, Celine;Siegel, Richard M.
Inactivated 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 GTTases 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 Tas-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.
