Indoleamine 2,3-dioxygenase-expressing dendritic cells are involved in the generation of CD4+CD25+ regulatory T cells in Peyer's patches in an orally tolerized, collagen-induced arthritis mouse model
- Equal contributors
1 The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Banpo-dong, Seocho-gu, Seoul 137-701, South Korea
2 Center for Rheumatic Disease, Division of Rheumatology, Department of Internal Medicine, Kangnam St Mary's Hospital, The Catholic University of Korea, Banpo-dong, Seocho-gu, Seoul 137-701, South Korea
3 Department of Hematology, Catholic Hematopoietic Stem Cell Transplantation, Youido St Mary's Hospital. The Catholic University of Korea, Youido-dong, Youngdungpo-Gu, Seoul 150-713, South Korea
Arthritis Research & Therapy 2008, 10:R11 doi:10.1186/ar2361
See related editorial by Toes and Wang, http://arthritis-research.com/content/10/2/108Published: 25 January 2008
The present study was devised to understand the role of systemic indoleamine 2,3-dioxygenase (IDO) in the tolerance induction for orally tolerized mice in collagen-induced arthritis (CIA). We examined whether IDO-expressing dendritic cells (DCs) are involved in the generation of CD4+CD25+ regulatory T cells during the induction of oral tolerance in a murine CIA model.
Type II collagen was fed six times to DBA/1 mice beginning 2 weeks before immunization, and the effect on arthritis was assessed. To examine the IDO expression, the DCs of messenger RNA and protein were analyzed by RT-PCR and Flow cytometry. In addition, a proliferative response assay was also carried out to determine the suppressive effects of DCs through IDO. The ability of DCs expressing IDO to induce CD4+CD25+ T regulatory cells was examined.
CD11c+ DCs in Peyer's patches from orally tolerized mice expressed a higher level of IDO than DCs from nontolerized CIA mice. IDO-expressing CD11c+ DCs were involved in the suppression of type II collagen-specific T-cell proliferation and in the downregulation of proinflammatory T helper 1 cytokine production. The suppressive effect of IDO-expressing CD11c+ DCs was mediated by Foxp3+CD4+CD25+ regulatory T cells.
Our data suggest that tolerogenic CD11c+ DCs are closely linked with the induction of oral tolerance through an IDO-dependent mechanism and that this pathway may provide a new therapeutic modality to treat autoimmune arthritis.