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

Abstract

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.

• Authors: Arnaud Couzinet, Kaoru Tamura, Hui-Min Chen, Keishiro Nishimura, Zhichao Wang, Yasuyuki Morishita, Kazuyoshi Takeda, Hideo Yagita, Hideyuki Yanai, Tadatsugu Taniguchi, Tomohiko Tamura
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 105 Issue 7 Pg. 2556-61 (Feb 19 2008) ISSN: 1091-6490 [Electronic] United States
• PMID: 18268344 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interferon Regulatory Factors
• Irf5 protein, mouse
• fas Receptor
• JNK Mitogen-Activated Protein Kinases
• Caspases

Topics

• Animals
• Apoptosis
• Caspases (metabolism)
• Down-Regulation
• Enzyme Activation
• Interferon Regulatory Factors (deficiency, genetics, metabolism)
• JNK Mitogen-Activated Protein Kinases (metabolism)
• Liver (metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Sensitivity and Specificity
• fas Receptor (metabolism)