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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, JingJung, In-HyukMoon, Shin HyeJeon, SejinJeong, Se-JinSonn, Seong-KeunSeo, SeungwoonLee, Mi-NiSong, Eun JuKweon, Hyae YonKim, SinaiKim, Tae KyeongKim, JuyangCho, Hong RaeChoi, Jae-HoonKwon, ByungsukOh, Goo Taeg
Ewha Authors
오구택손성근이미니서승운전세진
SCOPUS Author ID
오구택scopus; 손성근scopus; 이미니scopusscopus; 서승운scopusscopus; 전세진scopus
Issue Date
2020
Journal Title
CELL REPORTS
ISSN
2211-1247JCR Link
Citation
CELL REPORTS vol. 30, no. 12, pp. 4124 - +
Publisher
CELL PRESS
Indexed
SCIE; SCOPUS WOS 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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