A cell-type-specific requirement for IFN regulatory factor 5 (IRF5) in Fas-induced apoptosis

作者：Couzinet Arnaud; Tamura Kaoru; Chen Hui min; Nishimura Keishiro; Wang ZhiChao; Morishita Yasuyuki; Takeda Kazuyoshi; Yagita Hideo; Yanai Hideyuki; Taniguchi Tadatsugu^*; Tamura Tomohiko

来源：Proceedings of the National Academy of Sciences of the United States of America, 2008, 105(7): 2556-2561.

DOI：10.1073/pnas.0712295105

• death receptor
• programmed cell death
• transcription factor liver
• dendritic cell

Apoptosis is a highly regulated process of cell suicide that occurs during development, host defense, and pathophysiology. The transcription factor IFN regulatory factor 5 (IRF5), known to be involved in the activation of innate immune responses, recently has been shown to be critical for DNA damage-induced apoptosis and tumor suppression. Here, we report on a cell-type-specific role of IRF5 in promoting apoptosis upon signaling through the death receptor Fas (CD95/APO-1/TNFRSF6). In particular, we show that mice deficient in the Irf5 gene are resistant to hepatic apoptosis and lethality in response to the in vivo administration of a Fas-activating monoclonal antibody, and that IRF5 is involved in a stage of Fas signaling that precedes the activation of caspase 8 and c-Jun N-terminal kinase (JNK). In addition to hepatocytes, IRF5 is also required for apoptosis in dendritic cells activated by hypomethylated CpG but not in thymocytes and embryonic fibroblasts in vitro. Thus, these findings reveal a cell-type-specific function for IRF5 in the complex regulatory mechanism of death-receptor-induced apoptosis.

• 出版日期2008-2-19