CD137 Signaling Regulates Acute Colitis via RALDH2-Expressing CD11b-CD103+ DCs.
Cell Rep
; 30(12): 4124-4136.e5, 2020 03 24.
Article
em En
| MEDLINE
| ID: mdl-32209473
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-1α 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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células Dendríticas
/
Transdução de Sinais
/
Antígenos CD
/
Colite
/
Cadeias alfa de Integrinas
/
Antígeno CD11b
/
Aldeído Oxirredutases
/
Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral
Limite:
Animals
Idioma:
En
Revista:
Cell Rep
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Coréia do Sul