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	Deletion of Cflar in the epidermis results in TNFR1-dependent and -independent lethal dermatitis.
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	◎三浦亮介、朴雪花、三宅早苗、駒沢幸子、小池正人、内山安男、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	Previous studies have shown that cellular FLICE-inhibitory protein (cFLIP) prevents the development of dermatitis by blocking TNF-dependent apoptosis of keratinocytes. However, it is unclear whether TNF-independent signal might also promote the development of dermatitis in epidermis-specific Cflar-deficient (Cflar) mice. Here we show that Cflar;Tnfrsf1a-/- mice were born at the expected Mendelian ratio, but developed severe dermatitis and succumbed within 10 days after birth. Apoptotic keratinocytes and ectopic keratinization were detected in the epidermis, and numbers of proliferating basal cells were increased in Cflar;Tnfrsf1a-/- mice compared to Tnfrsf1a-/- mice along with the development of dermatitis. Epidermal differentiation markers, loricrin, fillagrin, and keratin (K)10, but not K5 were severely decreased in the skin of Cflar;Tnfrsf1a-/- mice at both mRNA and protein levels. Conversely, various inflammatory cytokines were elevated in the skin of Cflar;Tnfrsf1a-/- mice. Together, impaired barrier function of the skin promoted infection with commensal bacteria, resulting in further exacerbation of inflammation. Together, cFLIP suppresses TNFR1-dependent and -independent apoptosis of keratinocytes and promotes normal epidermal differentiation, thereby maintaining the skin homeostasis.