| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*Laboratory of Immunodynamics, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, Suita, Japan;
Laboratory of Gastrointestinal Immunology, World Premier International Immunology Frontier Research Center and
The 21st Century Center of Excellence Program, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan;
Age Dimension Research Center, National Institute for Advanced Industrial Science and Technology, Osaka, Japan;
¶Department of Microbiology, Kinki University School of Medicine, Osaka, Japan;
||Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan;
#National Institute for Longevity Sciences, Obu, Japan;
**Laboratory of Immunodynamics, World Premier International Immunology Frontier Research Center, Osaka University, Tsukuba, Japan; and
Division of Integrative Bioscience and Biotechnology, Pohang University of Science and Technology, Pohang, Korea
Dendritic cells (DCs) express the immunoregulatory enzyme IDO in response to certain inflammatory stimuli, but it is unclear whether DCs express this enzyme under steady-state conditions in vivo. In this study, we report that the DCs in mesenteric lymph nodes (MLNs) constitutively express functional IDO, which metabolizes tryptophan to kynurenine. In line with a previous report that regulatory T cells (Tregs) can induce IDO in DCs via the CTLA-4/B7 interaction, a substantial proportion of the MLN DCs were located in juxtaposition to Tregs, whereas this tendency was not observed for splenic DCs, which do not express IDO constitutively. When CTLA-4 was selectively deleted in Tregs, the frequency of IDO-expressing DCs in MLNs decreased significantly, confirming CTLA-4’s role in IDO expression by MLN DCs. We also found that the MLN DCs produced CCL22, which can attract Tregs via CCR4, and that the phagocytosis of autologous apoptotic cells induced CCL22 expression in CCL22 mRNA-negative DCs. Mice genetically deficient in the receptor for CCL22, CCR4, showed markedly reduced IDO expression in MLN-DCs, supporting the involvement of the CCL22/CCR4 axis in IDO induction. Together with our previous observation that MLN DCs contain much intracytoplasmic cellular debris in vivo, these results indicate that reciprocal interactions between the DCs and Tregs via both B7/CTLA-4 and CCL22/CCR4 lead to IDO induction in MLN DCs, which may be initiated and/or augmented by the phagocytosis of autologous apoptotic cells by intestinal DCs. Such a mechanism may help induce the specific milieu in MLNs that is required for the induction of oral tolerance.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan (18790338 and 19041044 to M.H.J.) and a grant for Advanced Research on Cancer from the Ministry of Education, Culture, Sports, Science and Technology of Japan (1701456 to M.M.).
2 Address correspondence and reprint requests to Dr. Myoung Ho Jang, Laboratory of Gastrointestinal Immunology, WPI Immunology Frontier Research Center, Osaka University, 3-1, Yamada-oka, Suita 565-0871, Japan and Dr. Masayuki Miyasaka, Laboratory of Immunodynamics, Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, C8, 2-2, Yamada-oka, Suita 565-0871, Japan. E-mail addresses: jang{at}frec.osaka-u.ac.jp and mmiyasak{at}orgctl.med.osaka-u.ac.jp
3 Abbreviations used in this paper: DC, dendritic cell; LP, lamina propria; Treg, regulatory T cells; MLN, mesenteric lymph node; SP, splenic; PP, Peyer’s patch; IEC, intestinal epithelial cell; PLN, peripheral lymph node; pAb, polyclonal Ab.
Related articles in The JI:
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
