ニシオ　ジュンコ   Nishio Junko   西尾　純子    所属   東邦大学  医学部 医学科    職種   准教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Essential contribution of IRF3 to intestinal homeostasis and microbiota-mediated Tslp gene induction.
掲載誌名	正式名：Proceedings of the National Academy of Sciences of the United States of America
掲載区分	国外
巻・号・頁	109(51),pp.21016-21
著者・共著者	Hideo Negishi,Shoji Miki,Hana Sarashina,Naoko Taguchi-Atarashi,Akira Nakajima,Kosuke Matsuki,Nobuyasu Endo,Hideyuki Yanai,Junko Nishio,Kenya Honda,Tadatsugu Taniguchi
発行年月	2012/12/18
概要	The large intestinal epithelial cells and immune cells are exposed to a variety of molecules derived from commensal microbiota that can activate innate receptors, such as Toll-like receptors (TLRs) and retinoic acid-inducible gene-I-like receptors (RLRs). Although the activation of these receptors is known to be critical for homeostasis of the large intestine, the underlying gene regulatory mechanisms are not well understood. Here, we show that IFN regulatory factor (IRF)3 is critical for the suppression of dextran sulfate sodium-induced colitis. IRF3-deficient mice exhibited lethal defects in the inflammatory and recovery phases of the colitis, accompanied by marked defects in the gene induction for thymic stromal lymphopoietin (TSLP), a cytokine known to be essential for protection of the large intestine. We further provide evidence that DNA and RNA of the large intestinal contents are critical for Tslp gene induction via IRF3 activation by cytosolic nucleic acid receptors. We also demonstrate that IRF3 indeed activates the gene promoter of Tslp via IRF-binding sequences. This newly identified intestinal gene regulatory mechanism, wherein IRF3 activated by microbiota-derived nucleic acids plays a critical role in intestinal homeostasis, may have clinical implication in colonic inflammatory disorders.
DOI	10.1073/pnas.1219482110
PMID	23213237