東京大学医科学研究所

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学友会セミナー

学友会セミナー:2012年12月7日

開催日時: 2012年12月7日 17:00-18:00
開催場所: Auditorium, 1st building
講師: Dr. Glen N. Barbar
所属: University of Miami School of Medicine
演題: "STING, the Sensing of Cytosolic DNA and Innate Immune-Mediated Inflammatory Disease."GCOE Program Seminar(Global Education Seminar)
概要:

Autoimmune diseases such as systemic lupus erythematosus (SLE) affect millions worldwide, the cause of which remains unknown. SLE and diseases such as Aicardi-Goutieres syndrome (AGS) are characterized by the overproduction of cytokines such as type I interferon (IFN) suggesting that stimulation of host innate immune responses, speculatively by chronic infection or self nucleic acids, play a role in the manifestation of these diseases. Mice lacking DNAse II die during embryonic development through comparable autoimmune disease since phagocytosed DNA from apoptotic cells cannot be adequately digested and intracellular host DNA sensors are activated resulting in the production of a variety of cytokines including type I IFN. The cellular sensor responsible for triggering DNA-mediated inflammation aggravated autoimmune disease remains to be determined. However, we report here that STING (Stimulator of Interferon Genes) complexes with phagocytosed undigested DNA and controls innate immune signaling events that facilitate such events. DNase II-dependent autoimmune embryonic lethality was rescued by loss of STING function and polyarthritis completely prevented since cytosolic DNA failed to robustly trigger cytokine production through STING controlled signaling pathways. Accordingly, loss of STING expression similarly alleviated Trex1-dependent lethal inflammatory myocarditis in mice, a model for AGS, speculatively caused by endogenous self DNA. Our data provides molecular insight into the causes of DNA-mediated inflammation-dependent autoimmune disorders and affords a new target that could plausibly be therapeutically controlled, to help prevent such diseases.

世話人: ○Taishin Akiyama (Division of Cellular and Molecular biology),
Kensuke Miyake (Division of Infectious Genetics )