| First Author | Li B | Year | 2015 |
| Journal | Nat Commun | Volume | 6 |
| Pages | 6131 | PubMed ID | 25607885 |
| Mgi Jnum | J:219712 | Mgi Id | MGI:5629609 |
| Doi | 10.1038/ncomms7131 | Citation | Li B, et al. (2015) IL-10 engages macrophages to shift Th17 cytokine dependency and pathogenicity during T-cell-mediated colitis. Nat Commun 6:6131 |
| abstractText | Polymorphisms attenuating IL-10 signalling confer genetic risk for inflammatory bowel disease. Yet, how IL-10 prevents mucosal autoinflammation is incompletely understood. We demonstrate using lineage-specific deletions of IL-10Ralpha that IL-10 acts primarily through macrophages to limit colitis. Colitis depends on IL-6 to support pathologic Th17 cell generation in wild-type mice. However, specific ablation of macrophage IL-10Ralpha provokes excessive IL-1beta production that overrides Th17 IL-6 dependency, amplifying the colonic Th17 response and disease severity. IL-10 not only inhibits pro-IL-1beta production transcriptionally in macrophages, but suppresses caspase-1 activation and caspase-1-dependent maturation of pro-IL-1beta to IL-1beta. Therefore, lineage-specific effects of IL-10 skew the cytokine dependency of Th17 cell development required for colitis pathogenesis. Coordinated interventions may be needed to fully suppress Th17-mediated immunopathology. |
