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

Bofeng Li; Prajwal Gurung; R K Subbarao Malireddi; Peter Vogel; Thirumala-Devi Kanneganti; Terrence L Geiger

doi:10.1038/ncomms7131

Back

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

Journal article

Open access

Peer reviewed

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

Bofeng Li, Prajwal Gurung, R K Subbarao Malireddi, Peter Vogel, Thirumala-Devi Kanneganti and Terrence L Geiger

Nature communications, Vol.6(1), pp.6131-6131

01/21/2015

DOI: 10.1038/ncomms7131

PMCID: PMC4302761

PMID: 25607885

Files and links (1)

url

https://doi.org/10.1038/ncomms7131View

Published (Version of record) Open Access

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.

Cytokines - metabolism

Inflammasomes

Signal Transduction

Colitis - genetics

Mice, Inbred C57BL

Caspase 1 - metabolism

Interleukin 1 Receptor Antagonist Protein - genetics

Risk

Inflammation

Inflammatory Bowel Diseases - metabolism

Colon - metabolism

Homeodomain Proteins - genetics

Mice, Knockout

Cell Lineage

Macrophages - metabolism

Animals

Th17 Cells - metabolism

Forkhead Transcription Factors - metabolism

Interleukin-1beta - metabolism

Colitis - metabolism

Interleukin-10 - metabolism

Mice

Transgenes

Details

Title: Subtitle: IL-10 engages macrophages to shift Th17 cytokine dependency and pathogenicity during T-cell-mediated colitis
Creators: Bofeng Li - Department of Pathology, St Jude Children's Research Hospital, 262 Danny Thomas Pl., Memphis, Tennesse 38105, USA
Prajwal Gurung - Department of Immunology, St Jude Children's Research Hospital, 262 Danny Thomas Pl., Memphis, Tennessee 38105, USA
R K Subbarao Malireddi - Department of Immunology, St Jude Children's Research Hospital, 262 Danny Thomas Pl., Memphis, Tennessee 38105, USA
Peter Vogel - Department of Pathology, St Jude Children's Research Hospital, 262 Danny Thomas Pl., Memphis, Tennesse 38105, USA
Thirumala-Devi Kanneganti - Department of Immunology, St Jude Children's Research Hospital, 262 Danny Thomas Pl., Memphis, Tennessee 38105, USA
Terrence L Geiger - Department of Pathology, St Jude Children's Research Hospital, 262 Danny Thomas Pl., Memphis, Tennesse 38105, USA
Resource Type: Journal article
Publication Details: Nature communications, Vol.6(1), pp.6131-6131
DOI: 10.1038/ncomms7131
PMID: 25607885
PMCID: PMC4302761
ISSN: 2041-1723
eISSN: 2041-1723
Grant note: R01 AI056153 / NIAID NIH HHS P30 CA021765 / NCI NIH HHS AI106600 / NIAID NIH HHS AI056153 / NIAID NIH HHS R56 AI106600 / NIAID NIH HHS
Language: English
Date published: 01/21/2015
Academic Unit: Infectious Diseases; Internal Medicine
Record Identifier: 9984094560202771

Metrics

19 Record Views

72 Times Cited - Web of Science