title: A distinct tolerogenic subset of splenic IDO(+)CD11b(+) dendritic cells from orally tolerized mice is responsible for induction of systemic immune tolerance and suppression of collagen-induced arthritis.
abstract: In oral tolerance, locally instigated tolerance in the gut propagate to systemic tolerance. In order to investigate the mechanism, we analyzed indoleamine 2,3-dioxygenase (IDO) expression in splenic dendritic cell (DC) subsets and tested whether DCs suppress collagen-induced arthritis (CIA) by inducing regulatory T cells (Tregs). The proportion of IDO-expressing cells was higher in the CD11b(+) subset of splenic DCs from orally tolerized CIA mice. These DCs suppressed type II collagen-specific T cell proliferation and promoted Treg induction from CD4(+)CD25(-) T cells using transforming growth factor-β. These DCs also increased the expression of cytotoxic T lymphocyte antigen-4 and programmed death-1 on Tregs. When adoptively transferred, spenic IDO-expressing CD11b(+) DCs from tolerized animals suppressed the development of arthritis, increased the Treg/Th17 cell ratio, and decreased the production of inflammatory cytokines in the spleen. Taken together, a distinct subset of splenic IDO(+)CD11b(+)DCs is responsible for the systemic immune regulation in oral tolerance.
authors.affiliation: The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Banpo-dong, Seocho-gu, Seoul 137-701, South Korea.
authors.forename: Min-Jung
authors.initials: MJ
authors.lastname: Park
authors.forename: Kyung-Su
authors.initials: KS
authors.lastname: Park
authors.forename: Hyun-Sil
authors.initials: HS
authors.lastname: Park
authors.forename: Mi-La
authors.initials: ML
authors.lastname: Cho
authors.forename: Sue-Yun
authors.initials: SY
authors.lastname: Hwang
authors.forename: So-Youn
authors.initials: SY
authors.lastname: Min
authors.forename: Mi-Kyung
authors.initials: MK
authors.lastname: Park
authors.forename: Sung-Hwan
authors.initials: SH
authors.lastname: Park
authors.forename: Ho-Youn
authors.initials: HY
authors.lastname: Kim
mesh_terms: D000284:Administration, Oral; D019264:Adoptive Transfer; D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000276:immunology; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D039481:CD11b Antigen / Q000235:genetics / Q000276:immunology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation; D024043:Collagen Type II; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D015870:Gene Expression; D007108:Immune Tolerance; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics / Q000276:immunology*; D039041:Integrin alpha4beta1 / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D009928:Organ Specificity; D061026:Programmed Cell Death 1 Receptor; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology
chemical_list: D000943:Antigens, Differentiation; D039481:CD11b Antigen; D024043:Collagen Type II; D016207:Cytokines; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D039041:Integrin alpha4beta1; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor; D016212:Transforming Growth Factor beta