연구논문

세부과제번호 2014M3A9D5A01073556 단계 1단계 3차년도
세부과제명 조직 및 세포수준에서 IMPC 마우스 간의 이차 대사표현형 분석기술 구축 공동 유/무 N
SCI여부 Y 게재년월 2016-07
논문제목 Exosome-mediated activation of toll-like receptor 3 in stellate cells stimulates interleukin-17 production by γδ T cells in liver fibrosis.
총저자명 Wonhyo SeoHyuk Soo EunSo Yeon KimHyon-Seung YiYoung-Sun LeeSeol-Hee ParkMi-Jin JangEunjung JoSun Chang KimYong-Mahn HanKeun-Gyu ParkWon-Il Jeong
학술지명 Hepatology 게재권(호) 64(2)
저널구분 - 페이지수 -
참여연구원 정원일 연구책임자 정원일
과제기여도 20 PMID 27178735
사사기관수 - IF (년도) 11.055
제1저자 서원효 교신저자 정원일
공동저자 -
초록
During liver injury, hepatocytes secrete exosomes that include diverse types of self-RNAs. Recently, self-noncoding RNA has been recognized as an activator of Toll-like receptor 3 (TLR3). However, the roles of hepatic exosomes and TLR3 in liver fibrosis are not yet fully understood. Following acute liver injury and early-stage liver fibrosis induced by a single or 2-week injection of carbon tetrachloride (CCl4 ), increased interleukin (IL)-17A production was detected primarily in hepatic γδ T cells in wild-type (WT) mice. However, liver fibrosis and IL-17A production by γδ T cells were both significantly attenuated in TLR3 knockout (KO) mice compared with WT mice. More interestingly, IL-17A-producing γδ T cells were in close contact with activated hepatic stellate cells (HSCs), suggesting a role for HSCs in IL-17A production by γδ T cells. In vitro treatments with exosomes derived from CCl4 -treated hepatocytes significantly increased the expression of IL-17A, IL-1β, and IL-23 in WT HSCs but not in TLR3 KO HSCs. Furthermore, IL-17A production by γδ T cells was substantially increased upon coculturing with exosome-treated WT HSCs or conditioned medium from TLR3-activated WT HSCs. However, similar increases were not detected when γδ T cells were cocultured with exosome-treated HSCs from IL-17A KO or TLR3 KO mice. Using reciprocal bone marrow transplantation between WT and TLR3 KO mice, we found that TLR3 deficiency in HSCs contributed to decreased IL-17A production by γδ T cells, as well as liver fibrosis.
다음글
이전글