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KMID : 0388220080150040306
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Journal of the Korean Rheumatism Association
2008 Volume.15 No. 4 p.306 ~ p.316
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Increased Indoleamine 2,3-Dioxygenase Expressing CD11c＋CD11b＋ Dendritic cells in Oral Tolerance to Type II Collagen
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Kim Young-Joo
Cho Mi-La
Kim Ho-Youn
Park Min-Jung
Park Hyun-Sil
Min So-Youn
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Abstract
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Objective: Indoleamine 2, 3-dioxygenase (IDO), an immuno suppression enzyme, is one of the initial and rate-limiting enzymes involved in the catabolism of the essential amino acid tryptophan. IDO inhibits T cell proliferation, induces T cell apoptosis, and plays a fundamental role in autoimmunity and allergy. We investigated which subtype of dendritic cells (DCs) is involved in IDO expression and the generation of regulatory T cells during the induction of oral tolerance in type II collagen-induced arthritis (CIA).
Methods: Type II Collagen was fed to DBA/1J mice before immunization. Changes in DC subtypes and induction of regulatory T cell in orally tolerized CIA mice were analyzed. Whether the effect of DC subtype was modulated by the IDO expression, was determined by flow cytometry (FACs) and confocal microscopy.
Results: IDO expression of CD11c＋ DCs was higher in orally tolerized CIA mice than in non-tolerized CIA mice. CD11b＋ DCs of the CD11c＋DCs, subtype was higher in the induction of in IDO expression. Our data suggest that these IDO expressing DCs of oral tolerized mice suppressed type II collagen-specific T cell proliferation and favored the differentiation of naive CD4＋ T cells into regulatory T cells. Especially, CD11c＋CD11b＋ DCs expressed IDO, which is known to be associated with regulatory T cell induction.
Conclusion: We observed that oral tolerance induced the increase in IDO-expressing CD11c＋CD11b＋ DCs, which appeared to induce regulatory T cells. IDO-expressing CD11c＋CD11b＋ DCs are involved in oral tolerance, which may provide a new therapeutic approach for the treatment of rheumatoid arthritis.
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KEYWORD
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CD11c＋CD11b＋ dendritic cells, Indoleamine 2, 3-dioxygenase (IDO), Oral tolerance, Regulatory T cell, Autoimmune arthritis
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