Cutting edge

Rac GTPases sensitize activated T cells to die via Fas

Madhu Ramaswamy, Celine Dumont, Anthony C. Cruz, Jagan R. Muppidi, Timothy S. Gomez, Daniel D Billadeau, Victor L J Tybulewicz, Richard M. Siegel

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)6384-6388
Number of pages5
JournalJournal of Immunology
Volume179
Issue number10
StatePublished - Nov 15 2007

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GTP Phosphohydrolases
Apoptosis
T-Lymphocytes
Plakins
Cell Death
Peripheral Tolerance
Immune Tolerance
Death Domain Receptors
rho GTP-Binding Proteins
Fas Ligand Protein
Protein Transport
RNA Interference
Autoimmune Diseases
Lymphocytes
Lipids

ASJC Scopus subject areas

  • Immunology

Cite this

Ramaswamy, M., Dumont, C., Cruz, A. C., Muppidi, J. R., Gomez, T. S., Billadeau, D. D., ... Siegel, R. M. (2007). Cutting edge: Rac GTPases sensitize activated T cells to die via Fas. Journal of Immunology, 179(10), 6384-6388.

Cutting edge : Rac GTPases sensitize activated T cells to die via Fas. / Ramaswamy, Madhu; Dumont, Celine; Cruz, Anthony C.; Muppidi, Jagan R.; Gomez, Timothy S.; Billadeau, Daniel D; Tybulewicz, Victor L J; Siegel, Richard M.

In: Journal of Immunology, Vol. 179, No. 10, 15.11.2007, p. 6384-6388.

Research output: Contribution to journalArticle

Ramaswamy, M, Dumont, C, Cruz, AC, Muppidi, JR, Gomez, TS, Billadeau, DD, Tybulewicz, VLJ & Siegel, RM 2007, 'Cutting edge: Rac GTPases sensitize activated T cells to die via Fas', Journal of Immunology, vol. 179, no. 10, pp. 6384-6388.
Ramaswamy M, Dumont C, Cruz AC, Muppidi JR, Gomez TS, Billadeau DD et al. Cutting edge: Rac GTPases sensitize activated T cells to die via Fas. Journal of Immunology. 2007 Nov 15;179(10):6384-6388.
Ramaswamy, Madhu ; Dumont, Celine ; Cruz, Anthony C. ; Muppidi, Jagan R. ; Gomez, Timothy S. ; Billadeau, Daniel D ; Tybulewicz, Victor L J ; Siegel, Richard M. / Cutting edge : Rac GTPases sensitize activated T cells to die via Fas. In: Journal of Immunology. 2007 ; Vol. 179, No. 10. pp. 6384-6388.
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