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.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Park
Min-Jung
MJ
The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Banpo-dong, Seocho-gu, Seoul 137-701, South Korea. pppmj22@catholic.ac.kr
Min
So-Youn
SY
Park
Kyung-Su
KS
Cho
Young-Gyu
YG
Cho
Mi-La
ML
Jung
Young-Ok
YO
Park
Hyun-Sil
HS
Chang
Soog-Hee
SH
Cho
Seok Goo
SG
Min
Jun-Ki
JK
Park
Sung-Hwan
SH
Kim
Ho-Youn
HY
D000284:Administration, Oral; D000818:Animals; D001169:Arthritis, Experimental / Q000201:enzymology* / Q000276:immunology* / Q000517:prevention & control; D039521:CD11c Antigen / Q000378:metabolism; D049109:Cell Proliferation; D016922:Cellular Senescence; D024043:Collagen Type II / Q000008:administration & dosage / Q000276:immunology; D003713:Dendritic Cells / Q000201:enzymology / Q000276:immunology*; D007108:Immune Tolerance; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism*; D051379:Mice; D008811:Mice, Inbred DBA; D009055:Mouth / Q000276:immunology; D010581:Peyer's Patches / Q000276:immunology* / Q000473:pathology; D010641:Phenotype; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology
D039521:CD11c Antigen; D024043:Collagen Type II; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D053645:Interleukin-2 Receptor alpha Subunit