Inhibition of Notch1 induces population and suppressive activity of regulatory T cell in inflammatory arthritis

Bo Youn Choi, Yuri Choi, Jong Sung Park, Li Jung Kang, Seung Hyun Baek, Jin Su Park, Gahee Bahn, Yoonsuk Cho, Hark Kyun Kim, Jihoon Han, Jae Hoon Sul, Sang Ha Baik, Dong Hoon Hyun, Thiruma V. Arumugam, Siyoung Yang, Jeung Whan Han, Young Mo Kang, Yong Woo Cho, Jae Hyung Park, Dong Gyu Jo

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

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 γ-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: γ-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.

Original languageEnglish
Pages (from-to)4795-4804
Number of pages10
JournalTheranostics
Volume8
Issue number17
DOIs
StatePublished - 2018

Keywords

  • CAIA
  • CIA
  • Notch1
  • Rheumatoid arthritis
  • Treg
  • γ-secretase

Fingerprint

Dive into the research topics of 'Inhibition of Notch1 induces population and suppressive activity of regulatory T cell in inflammatory arthritis'. Together they form a unique fingerprint.

Cite this