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Blood. 2009 Aug 13;114(7):1355-65. doi: 10.1182/blood-2008-11-189118. Epub 2009 Jun 15.

Regulation of Fas-mediated immune homeostasis by an activation-induced protein, Cyclon.

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Department of Pathology, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY, USA.


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 the key cell surface proteins that mediate AICD in CD4(+) and CD8(+) T cells. Despite 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 on T-cell receptor ligation and important for immune homeostasis. Transgenic expression of Cyclon ameliorated autoimmune phenotype in mice lacking subunits of 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 show reduced AICD and expression of Fas, indicating a critical role of Cyclon in Fas expression in activated T cells. We think that our data provide insight into expression regulation of Fas in T cells.

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