| First Author | Jin J | Year | 2020 |
| Journal | Cell Rep | Volume | 30 |
| Issue | 12 | Pages | 4124-4136.e5 |
| PubMed ID | 32209473 | Mgi Jnum | J:288258 |
| Mgi Id | MGI:6416655 | Doi | 10.1016/j.celrep.2020.02.103 |
| Citation | Jin J, et al. (2020) CD137 Signaling Regulates Acute Colitis via RALDH2-Expressing CD11b(-)CD103(+) DCs. Cell Rep 30(12):4124-4136.e5 |
| abstractText | 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-1alpha 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. |
