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.

Min, So Youn; Park, Min Jung; Park, Kyung Su; La Cho, Mi; Park, Hyun Sil; Lee, Seon Yeong; Park, Mi Kyung; Cho, Young-Gyu; Lee, Sang Haak; Lee, Sang Heon; Kim, Ho Youn

Dendritic cells (DCs) play an important role in maintaining self-tolerance. Recent evidence demonstrates that indoleamine 2,3-dioxygenase (IDO), which is involved in tryptophan catabolism, is produced by DCs and plays an important role in the regulation of T cell immunity. We examined whether IDO-expressing DCs are involved in the generation of CD4 CD25 regulatory T cells during the induction of oral tolerance in a murine collagen-induced arthritis (CIA) model. CD11c DCs in Peyer's patches from orally tolerized mice expressed a higher level of IDO than DCs from nontolerized CIA mice did. IDO-expressing CD11c DCs were involved in the suppression of type II collagen-specific T cell proliferation and 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.

FASEB Journal, 2008, Vol 22, p390

0892-6638

Academic Journal

10.1096/fasebj.22.2_supplement.390