Immunoregulatory function of PIR-A/B+ DCs in the inflammatory responses of dextran sodium sulfate-induced colitis |
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Authors: | Akiko Kurishima Muneo Inaba Yutaku Sakaguchi Toshiro Fukui Kazushige Uchida Akiyoshi Nishio Shosaku Nomura Kazuichi Okazaki |
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Institution: | 1. Division of Gastroenterology and Hepatology, Third Department of Internal Medicine, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi, Osaka, 570-8506, Japan 2. First Department of Internal Medicine, Kansai Medical University, Osaka, Japan
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Abstract: | Background Dendritic cells (DCs) may play an important role in forms of inflammatory bowel disease (IBD), such as Crohn’s disease and ulcerative colitis. DCs are generally recognized as initiators of acquired immunity and also serve as regulators of both innate and acquired immunity. We used the animal model of colitis induced by dextran sodium sulfate (DSS), and examined whether DCs prepared from the colon show immunoregulatory roles in the termination of DSS-induced colitis. Methods C57BL/6 mice exposed to DSS for 5 days developed acute colitis. DCs were isolated from the large intestinal lamina propria, and then analyzed for phenotypical, functional, and genetic data. Results Only PIR-A/Blow conventional DCs (cDCs) were detected in the steady state. However, after the treatment of DSS, PIR-A/Bhigh cDCs appeared and gradually increased from day 5 to day 7, at which time the DSS-induced colitis was terminated. Then, allogeneic mixed leukocyte reaction (MLR) was performed. The stimulatory activity of PIR-A/Bhigh cDCs obtained on day 7 was very low, and the addition of PIR-A/Bhigh cDCs suppressed the T cell proliferation in MLR, indicating the immunoregulatory role of PIR-A/Bhigh cDCs. The immunoregulatory role of PIR-A/Bhigh cDCs was confirmed by the in vivo transfer experiment, showing their therapeutic effect on DSS-induced colitis. The message level of TGFβi was significantly higher in PIR-A/Bhigh cDCs, while that of IFN-γ was highly upregulated in PIR-A/Blow cDCs, being well in accordance with the fact that PIR-A/Bhigh cDCs showed a suppressive function against activated T cells. Conclusion PIR-A/Bhigh cDCs showed a suppressive function against activated T cells by producing inhibitory cytokines. |
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