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IL-10 engages macrophages to shift Th17 cytokine dependency and pathogenicity during T-cell-mediated colitis

Author

Listed:
  • Bofeng Li

    (St Jude Children’s Research Hospital)

  • Prajwal Gurung

    (St Jude Children’s Research Hospital)

  • R. K. Subbarao Malireddi

    (St Jude Children’s Research Hospital)

  • Peter Vogel

    (St Jude Children’s Research Hospital)

  • Thirumala-Devi Kanneganti

    (St Jude Children’s Research Hospital)

  • Terrence L. Geiger

    (St Jude Children’s Research Hospital)

Abstract

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-10Rα 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-10Rα provokes excessive IL-1β production that overrides Th17 IL-6 dependency, amplifying the colonic Th17 response and disease severity. IL-10 not only inhibits pro-IL-1β production transcriptionally in macrophages, but suppresses caspase-1 activation and caspase-1-dependent maturation of pro-IL-1β to IL-1β. 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.

Suggested Citation

  • Bofeng Li & Prajwal Gurung & R. K. Subbarao Malireddi & Peter Vogel & Thirumala-Devi Kanneganti & Terrence L. Geiger, 2015. "IL-10 engages macrophages to shift Th17 cytokine dependency and pathogenicity during T-cell-mediated colitis," Nature Communications, Nature, vol. 6(1), pages 1-13, May.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7131
    DOI: 10.1038/ncomms7131
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