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IL-10 signaling in dendritic cells controls IL-1β-mediated IFNγ secretion by human CD4+T cells: relevance to inflammatory bowel disease
- Source :
- Mucosal immunology; September 2019, Vol. 12 Issue: 5 p1201-1211, 11p
- Publication Year :
- 2019
-
Abstract
- Uncontrolled interferon γ (IFNγ)-mediated T-cell responses to commensal microbiota are a driver of inflammatory bowel disease (IBD). Interleukin-10 (IL-10) is crucial for controlling these T-cell responses, but the precise mechanism of inhibition remains unclear. A better understanding of how IL-10 exerts its suppressive function may allow identification of individuals with suboptimal IL-10 function among the heterogeneous population of IBD patients. Using cells from patients with an IL10RAdeficiency or STAT3mutations, we demonstrate that IL-10 signaling in monocyte-derived dendritic cells (moDCs), but not T cells, is essential for controlling IFNγ-secreting CD4+T cells. Deficiency in IL-10 signaling dramatically increased IL-1β release by moDCs. IL-1β boosted IFNγ secretion by CD4+T cells either directly or indirectly by stimulating moDCs to secrete IL-12. As predicted a signature of IL-10 dysfunction was observed in a subgroup of pediatric IBD patients having higher IL-1β expression in activated immune cells and macroscopically affected intestinal tissue. In agreement, reduced IL10RAexpression was detected in peripheral blood mononuclear cells and a subgroup of pediatric IBD patients exhibited diminished IL-10 responsiveness. Our data unveil an important mechanism by which IL-10 controls IFNγ-secreting CD4+T cells in humans and identifies IL-1β as a potential classifier for a subgroup of IBD patients.
Details
- Language :
- English
- ISSN :
- 19330219 and 19353456
- Volume :
- 12
- Issue :
- 5
- Database :
- Supplemental Index
- Journal :
- Mucosal immunology
- Publication Type :
- Periodical
- Accession number :
- ejs62071664
- Full Text :
- https://doi.org/10.1038/s41385-019-0194-9