Inhibition of Notch1 induces population and suppressive activity of regulatory T cell in inflammatory arthritis
- 주제(키워드) rheumatoid arthritis , Notch1 , Treg , CIA , CAIA , gamma-secretase
- 주제(기타) Medicine, Research & Experimental
- 설명문(일반) [Choi, Bo Youn; Choi, Yuri; Park, Jong-Sung; Baek, Seung Hyun; Park, Jin Su; Bahn, Gahee; Cho, Yoonsuk; Kim, Hark Kyun; Han, Jihoon; Sul, Jae Hoon; Baik, Sang-Ha; Arumugam, Thiruma V.; Han, Jeung-Whan; Jo, Dong-Gyu] Sungkyunkwan Univ, Sch Pharm, Suwon, South Korea; [Kang, Li-Jung; Yang, Siyoung] Ajou Univ, Sch Med, Dept Pharmacol, Suwon, South Korea; [Park, Jin Su; Park, Jae Hyung; Jo, Dong-Gyu] Sungkyunkwan Univ, Samsung Adv Inst Hlth Sci & Technol, Dept Hlth Sci & Technol, Seoul, South Korea; [Baik, Sang-Ha; Arumugam, Thiruma V.] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Physiol, Singapore, Singapore; [Hyun, Dong Hoon] Ewha Womans Univ, Dept Life Sci, Seoul, South Korea; [Kang, Young Mo] Kyungpook Natl Univ, Sch Med, Dept Internal Med Rheumatol, Daegu, South Korea; [Cho, Yong-Woo] Hanyang Univ, Dept Chem Engn, Ansan, South Korea; [Park, Jae Hyung] Sungkyunkwan Univ, Coll Engn, Suwon, South Korea; [Park, Jae Hyung; Jo, Dong-Gyu] Sungkyunkwan Univ, Biomed Inst Convergence, Suwon, South Korea
- 등재 SCIE, SCOPUS
- 발행기관 IVYSPRING INT PUBL
- 발행년도 2018
- URI http://www.dcollection.net/handler/ewha/000000156271
- 본문언어 영어
- Published As http://dx.doi.org/10.7150/thno.26093
초록/요약
Inhibition of Notch signalling has shown anti-inflammatory properties in vivo and in vitro models of rheumatoid arthritis (RA). The objective of this study was to determine whether Notch1 might play a role in regulating T-regulatory cells (Tregs) in animal models of RA. Methods: Collagen-induced arthritis (CIA) and collagen antibody-induced arthritis (CAIA) were induced in C57BL/6, Notch1 antisense transgenic (NAS) or DBA1/J mice. We examined whether pharmacological inhibitors of gamma-secretase (an enzyme required for Notch1 activation) and antisense-mediated knockdown of Notch1 could attenuate the severity of inflammatory arthritis in CIA and CAIA mice. Proportions of CD4(+)CD25(+)Foxp3(+) Treg cells were measured by flow cytometry. To assess the suppressive capacity of Treg toward responder cells, CFSE-based suppression assay of Treg was performed. Results: gamma-secretase inhibitors and antisense-mediated knockdown of Notch1 reduced the severity of inflammatory arthritis in both CIA and CAIA mice. Pharmacological and genetic inhibition of Notch1 signalling induced significant elevation of Treg cell population in CIA and CAIA mice. We also demonstrated that inhibition of Notch signalling suppressed the progression of inflammatory arthritis through modulating the expansion and suppressive function of regulatory T (Treg) cells. Conclusion: Pharmacological and genetic inhibition of Notch1 signalling suppresses the progression of inflammatory arthritis through modulating the population and suppressive function of Treg cells in animal models of RA.
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