Indoleamine 2,3-dioxygenase-expressing dendritic cells are involved in the generation of CD4 CD25 regulatory T cells in Peyers patches in an orally tolerized, collagen-induced arthritis mouse modelReportar como inadecuado




Indoleamine 2,3-dioxygenase-expressing dendritic cells are involved in the generation of CD4 CD25 regulatory T cells in Peyers patches in an orally tolerized, collagen-induced arthritis mouse model - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Arthritis Research and Therapy

, 10:R11

First Online: 25 January 2008Received: 12 April 2007Revised: 17 January 2008Accepted: 25 January 2008

Abstract

IntroductionThe 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 CD4CD25 regulatory T cells during the induction of oral tolerance in a murine CIA model.

MethodsType 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 CD4CD25 T regulatory cells was examined.

ResultsCD11c 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 Foxp3CD4CD25 regulatory T cells.

ConclusionOur 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.

AbbreviationsAPC= antigen-presenting cell

bp= base pair

CIA= collagen-induced arthritis

CII= type II collagen

cpm= counts per minute

DC= dendritic cell

ELISA= enzyme-linked immunosorbent assay

IDO = indoleamine 23-dioxygenase

IFN= interferon

IL= interleukin

1-MT= 1-methyl tryptophan

mAb= monoclonal antibody

MHC= major histocompatibility complex

PBS= phosphate-buffered saline

PCR= polymerase chain reaction

RT= reverse transcriptase

TGFβ= transforming growth factor beta.

Electronic supplementary materialThe online version of this article doi:10.1186-ar2361 contains supplementary material, which is available to authorized users.

Min-Jung Park, So-Youn Min contributed equally to this work.

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Autor: Min-Jung Park - So-Youn Min - Kyung-Su Park - Young-Gyu Cho - Mi-La Cho - Young-Ok Jung - Hyun-Sil Park - Soog-Hee Chang -

Fuente: https://link.springer.com/



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