ナカノ　ヒロヤス   Nakano Hiroyasu   中野　裕康    所属   東邦大学  医学部 医学科    東邦大学  医学部 医学科    職種   教授
言語種別	日本語
発表タイトル	Intestinal epithelial cell (IEC)-specific Cflar-deficient mice spontaneously develop TNFR1-independent ileitis
会議名	細胞競合・ダイイングコード合同若手ワークショップ
主催者	新学術領域　細胞競合・ダイイングコード
発表形式	ポスター掲示
講演区分	一般
発表者・共同発表者	◎片桐翔治、朴雪花、中野　裕康
発表年月日	2017/01/17
開催地 （都市, 国名）	大阪府大阪市ホテルコスモスクエア国際交流センター
概要	Cellular FLICE-inhibitory protein (cFLIP) that is encoded by Cflar gene regulates tissue homeostasis by preventing necroptosis and apoptosis. We previously reported that intestinal epithelial cell (IEC)-specific Cflar-deficient (CflarIEC-KO) mice die soon after birth due to severe apoptosis of IECs. To elucidate contribution of TNFR1-dependent signal to apoptosis of IECs of CflarIEC-KO mice, here we generated CflarIEC-KO;Tnfr1-/- mice. While perinatal lethality of CflarIEC-KO mice was partially rescued by deletion of Tnfr1 gene, but all CflarIEC-KO;Tnfr1-/- mice spontaneously developed ileitis, but to a lesser extent colitis, due to an increase in numbers of apoptotic cells. We found that expression of antimicrobial protein Reg3b was severely downregulated in the small intestine of CflarIEC-KO;Tnfr1-/- mice compared to Tnfr1-/- mice at both mRNA and protein levels. Conversely, expression of Reg3b and Reg3g was elevated in the colon of CflarIEC-KO;Tnfr1-/- mice compared to Tnfr1-/- mice. Moreover, perinatal lethality of CflarIEC-KO mice was partially rescued by deletion of Ripk3 gene, but CflarIEC-KO;Ripk3-/- mice similarly developed ileitis. Thus, cFLIP protects the development of ileitis by preventing TNFR1-independent but RIPK3-dependent cell death of IECs.