A role for CD47 in the development of experimental colitis mediated by SIRPα+CD103− dendritic cells
Open Access
- 24 August 2009
- journal article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 206 (9), 1995-2011
- https://doi.org/10.1084/jem.20082805
Abstract
Mesenteric lymph node (mLN) CD103 (αE integrin)+ dendritic cells (DCs) induce regulatory T cells and gut tolerance. However, the function of intestinal CD103− DCs remains to be clarified. CD47 is the ligand of signal regulatory protein α (SIRPα) and promotes SIRPα+ myeloid cell migration. We first show that mucosal CD103− DCs selectively express SIRPα and that their frequency was augmented in the lamina propria and mLNs of mice that developed Th17-biased colitis in response to trinitrobenzene sulfonic acid. In contrast, the percentage of SIRPα+CD103− DCs and Th17 responses were decreased in CD47-deficient (CD47 knockout [KO]) mice, which remained protected from colitis. We next demonstrate that transferring wild-type (WT), but not CD47 KO, SIRPα+CD103− DCs in CD47 KO mice elicited severe Th17-associated wasting disease. CD47 expression was required on the SIRPα+CD103− DCs for efficient trafficking to mLNs in vivo, whereas it was dispensable on both DCs and T cells for Th17 polarization in vitro. Finally, administration of a CD47-Fc molecule resulted in reduced SIRPα+CD103− DC–mediated Th17 responses and the protection of WT mice from colitis. We thus propose SIRPα+CD103− DCs as a pathogenic DC subset that drives Th17-biased responses and colitis, and the CD47–SIRPα axis as a potential therapeutic target for inflammatory bowel disease.Keywords
This publication has 69 references indexed in Scilit:
- Intestinal epithelial cells promote colitis-protective regulatory T-cell differentiation through dendritic cell conditioningMucosal Immunology, 2009
- Blood-derived inflammatory dendritic cells in lymph nodes stimulate acute T helper type 1 immune responsesNature Immunology, 2009
- Late Developmental Plasticity in the T Helper 17 LineageImmunity, 2009
- Dendritic cells in intestinal immune regulationNature Reviews Immunology, 2008
- Differential regulation of central nervous system autoimmunity by TH1 and TH17 cellsNature Medicine, 2008
- Lamina propria macrophages and dendritic cells differentially induce regulatory and interleukin 17–producing T cell responsesNature Immunology, 2007
- Th17: the third member of the effector T cell trilogyCurrent Opinion in Immunology, 2007
- Monocytes give rise to mucosal, but not splenic, conventional dendritic cellsThe Journal of Experimental Medicine, 2006
- Expression of the self-marker CD47 on dendritic cells governs their trafficking to secondary lymphoid organsThe EMBO Journal, 2006
- Isolation and Purification of Colon Lamina Propria Dendritic Cells from Mice with ColitisCytotechnology, 2004