Submitted November 12, 2008
Accepted June 6, 2009
Regulation of Fas-mediated immune homeostasis by an activation-induced protein, Cyclon
Shella Saint Fleur, Akemi Hoshino, Kimie Kondo, Takeshi Egawa, and Hodaka Fujii*
Department of Pathology, New York University School of Medicine, New York, NY, United States
Molecular Pathogenesis Program, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY, United States
Combined Program on Microbiology and Immunology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan
* Corresponding author; email: hodaka{at}biken.osaka-u.ac.jp.
Activation-induced cell death (AICD) plays an essential role in the contraction of activated T cells after eradication of pathogen. Fas (APO-1 / CD95) is one of key cell surface proteins that mediate AICD in CD4 (+) and CD8 (+) T cells. In spite of its prime importance in cell death, regulation of Fas expression in T cells is poorly understood. Here we show that Cyclon, a newly identified cytokine-inducible protein, is induced in T cells upon T cell receptor (TCR) ligation and important for immune homeostasis. Transgenic expression of Cyclon ameliorated autoimmune phenotype in mice lacking subunits of interleukin-2 receptor (IL-2R). Transgenic expression of Cyclon markedly enhanced AICD through increased expression of Fas whose expression is essential for Cyclon action. Finally, we demonstrated that activated but not resting CD4 (+) T cells with targeted deletion of a Cyclon allele showed reduced AICD and expression of Fas, indicating a critical role of Cyclon in Fas expression in activated T cells. We believe that our data provide insight into expression regulation of Fas in T cells.
