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 Jung Park, So Youn Min, Kyung Su Park, Young Gyu Cho, Mi La Cho, Young Ok Jung, Hyun Sil Park, Soog Hee Chang, Seok G. Cho, Jun Ki Min, Sung Hwan Park, Ho Youn Kim

Research output: Contribution to journalArticle

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Abstract

Introduction: 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. Conclusion: 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.

Original languageEnglish (US)
Article numberR11
JournalArthritis Research and Therapy
Volume10
Issue number1
DOIs
StatePublished - Jan 25 2008

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Indoleamine-Pyrrole 2,3,-Dioxygenase
Peyer's Patches
Experimental Arthritis
Regulatory T-Lymphocytes
Dendritic Cells
Collagen Type II
Arthritis
Inbred DBA Mouse
Immunization
Flow Cytometry
Down-Regulation
Cell Proliferation
Cytokines
T-Lymphocytes
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Rheumatology
  • Medicine(all)

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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. / Park, Min Jung; Min, So Youn; Park, Kyung Su; Cho, Young Gyu; Cho, Mi La; Jung, Young Ok; Park, Hyun Sil; Chang, Soog Hee; Cho, Seok G.; Min, Jun Ki; Park, Sung Hwan; Kim, Ho Youn.

In: Arthritis Research and Therapy, Vol. 10, No. 1, R11, 25.01.2008.

Research output: Contribution to journalArticle

Park, Min Jung ; Min, So Youn ; Park, Kyung Su ; Cho, Young Gyu ; Cho, Mi La ; Jung, Young Ok ; Park, Hyun Sil ; Chang, Soog Hee ; Cho, Seok G. ; Min, Jun Ki ; Park, Sung Hwan ; Kim, Ho Youn. / 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. In: Arthritis Research and Therapy. 2008 ; Vol. 10, No. 1.
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abstract = "Introduction: 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. Conclusion: 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.",
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AU - Park, Min Jung

AU - Min, So Youn

AU - Park, Kyung Su

AU - Cho, Young Gyu

AU - Cho, Mi La

AU - Jung, Young Ok

AU - Park, Hyun Sil

AU - Chang, Soog Hee

AU - Cho, Seok G.

AU - Min, Jun Ki

AU - Park, Sung Hwan

AU - Kim, Ho Youn

PY - 2008/1/25

Y1 - 2008/1/25

N2 - Introduction: 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. Conclusion: 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.

AB - Introduction: 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. Conclusion: 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.

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