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CD137 Signaling Regulates Acute Colitis via RALDH2-Expressing CD11b(-)CD103(+) DCs
- Title
- CD137 Signaling Regulates Acute Colitis via RALDH2-Expressing CD11b(-)CD103(+) DCs
- 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
- Ewha Authors
- 오구택; 손성근; 이미니; 서승운; 전세진
- SCOPUS Author ID
- 오구택; 손성근; 이미니; 서승운; 전세진
- Issue Date
- 2020
- Journal Title
- CELL REPORTS
- ISSN
- 2211-1247
- Citation
- CELL REPORTS vol. 30, no. 12, pp. 4124 - +
- Publisher
- CELL PRESS
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- 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.
- DOI
- 10.1016/j.celrep.2020.02.103
- Appears in Collections:
- 자연과학대학 > 생명과학전공 > Journal papers
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