CD137 Signaling Regulates Acute Colitis via RALDH2-Expressing CD11b−CD103+ DCsopen access
- Authors
- Jin, Jing; Jung, In-Hyuk; Moon, Shin Hye; Jeon, Sejin; Jeong, Se-Jin; Sonn, Seong-Keun; Seo, Seungwoon; Lee, Mi-Ni; Song, Eun Ju; Kweon, Hyae Yon; Kim, Sinai; Kim, Tae Kyeong; Kim, Juyang; Cho, Hong Rae; Choi, Jae-Hoon; Kwon, Byungsuk; Oh, Goo Taeg
- Issue Date
- Mar-2020
- Publisher
- CELL PRESS
- Keywords
- acute colitis; CD137; Foxp3+ Treg; IL-23; immune checkpoint; immune tolerance; RALDH2; regulatory CD11b?CD103+ DC; retinoic acid; TH17
- Citation
- CELL REPORTS, v.30, no.12, pp.4124 - 4136
- Indexed
- SCIE
SCOPUS
- Journal Title
- CELL REPORTS
- Volume
- 30
- Number
- 12
- Start Page
- 4124
- End Page
- 4136
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/10668
- DOI
- 10.1016/j.celrep.2020.02.103
- ISSN
- 2211-1247
- Abstract
- CD137, a potent costimulatory receptor for CD8(+) T cells, is expressed in various non-T cells, but little is known about its regulatory functions in these cells. In this study, we show that CD137 signaling, specifically in intestinal CD11b(-)CD103(+) dendritic cells (DCs), restricts acute colitis progression. Mechanistically, CD137 engagement activates TAK1 and subsequently stimulates the AMPK-PGC-1 alpha axis to enhance expression of the Aldh1a2 gene encoding the retinoic acid (RA) metabolizing enzyme RALDH2. RA can act on CD11b(+)CD103(-) DCs and induce SOCS3 expression, which, in turn, suppresses p38MAPK activation and interleukin-23 (IL-23) production. Administration of RA in DC-specific CD137(-/-) mice represses IL-23-producing CD11b(+)CD103(-) DCs and TH17 cells, indicating that RA is a major inhibitory effector molecule against intestinal CD11b(+)CD103(-) DCs. Additionally, the therapeutic effect of the anti-CD137 antibody is abrogated in DC-specific CD137(-/-) mice. Taken together, our results define a mechanism of paracrine immunoregulation operating between adjacent DC subsets in the intestine.
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