CD137 Signaling Regulates Acute Colitis via RALDH2-Expressing CD11b(-)CD103(+) DCs
- 주제(기타) Cell Biology
- 설명문(일반) [Jin, Jing; Moon, Shin Hye; Jeon, Sejin; Sonn, Seong-Keun; Seo, Seungwoon; Lee, Mi-Ni; Song, Eun Ju; Kweon, Hyae Yon; Kim, Sinai; Kim, Tae Kyeong; Oh, Goo Taeg] Ewha Womans Univ, Immune & Vasc Cell Network Res Ctr, Dept Life Sci, Natl Creat Initiatives, Seoul 120750, South Korea; [Jung, In-Hyuk; Jeong, Se-Jin] Washington Univ, Dept Med, Cardiovasc Div, Sch Med, St Louis, MO 63110 USA; [Kim, Juyang; Kwon, Byungsuk] Univ Ulsan, Sch Biol Sci, Ulsan 44610, South Korea; [Kim, Juyang; Kwon, Byungsuk] Univ Ulsan, Biomed Res Ctr, Ulsan 44610, South Korea; [Cho, Hong Rae] Univ Ulsan, Ulsan Univ Hosp, Coll Med, Dept Surg, Ulsan 44610, South Korea; [Cho, Hong Rae] Univ Ulsan, Ulsan Univ Hosp, Coll Med, Biomed Res Ctr, Ulsan 44610, South Korea; [Choi, Jae-Hoon] Hanyang Univ, Coll Nat Sci, Res Inst Nat Sci, Dept Life Sci, Seoul 133791, South Korea
- 등재 SCIE, SCOPUS
- OA유형 gold
- 발행기관 CELL PRESS
- 발행년도 2020
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000168764
- 본문언어 영어
- Published As https://dx.doi.org/10.1016/j.celrep.2020.02.103
- PubMed https://pubmed.ncbi.nlm.nih.gov/32209473
초록/요약
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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