Deletion of Cflip in the epidermis results in TNFR1-dependent and independent lethal dermatitis

2015 Fiscal Year Final Research Report

• Project/Area Number: 26893265
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Dermatology
• Research Institution: Toho University
• Principal Investigator: PIAO Xuehua 東邦大学, 医学部, 博士研究員 (70739812)
• Project Period (FY): 2014-08-29 – 2016-03-31
• Keywords: 皮膚炎 / 細胞死 / apoptosis / ケラチノサイト / cFLIP / バリア機能 / 皮膚の分化 / TNF

Outline of Final Research Achievements

Cellular FLICE-inhibitory protein (cFLIP) is a protease-inactivate caspase 8 homologue that binds to caspase 8 and blocks apoptosis. Recent studies have shown that cFLIP prevents TNFα-induced apoptosis of keratinocytes by using inducible keratinocyte-specific Cflip-deficient mice (Weinlich et al., Cell Rep. 2013; Panayotova-Domitrova et al., Cell Rep. 2013). However, it is unclear whether TNFα-independent pathway might contribute to keratinocyte apoptosis in Cflip-deficient mice. Here we show that epidermis-specific Cflip-deficient mice (CflipE-KO) die in utero. Intriguingly, CflipE-KO;Tnfr1-/- mice were born at the expected Mendelian ratio, but still developed severe dermatitis soon after birth. Enhanced apoptosis and a defect in differentiation of keratinocytes were observed inCflipE-KO;Tnfr1-/- mice. Together, cFLIP plays a crucial role in protection of keratinocytes from TNFR1-dependent and -independent apoptosis.

Free Research Field

皮膚疾患