ID | 65531 |
フルテキストURL | |
著者 |
Furuta, Kazuyuki
Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
Onishi, Hiroka
Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
Ikada, Yuki
Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
Masaki, Kento
Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
Tanaka, Satoshi
Department of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University
Kaito, Chikara
Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
ORCID
Kaken ID
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抄録 | Dendritic cells (DCs) present foreign antigens to T cells via the major histocompatibility complex (MHC), thereby inducing acquired immune responses. ATP accumulates at sites of inflammation or in tumor tissues, which triggers local inflammatory responses. However, it remains to be clarified how ATP modulates the functions of DCs. In this study, we investigated the effects of extracellular ATP on mouse bone marrow- derived dendritic cells (BMDCs) as well as the potential for subsequent T cell activation. We found that high concentrations of ATP (1 mM) upregulated the cell surface expression levels of MHC-I, MHC-II, and co-stimulatory molecules CD80 and CD86 but not those of co-inhibitory molecules PD-L1 and PD-L2 in BMDCs. Increased surface expression of MHC-I, MHC-II, CD80, and CD86 was inhibited by a pan-P2 receptor antagonist. In addition, the upregulation of MHC-I and MHC-II expression was inhibited by an adenosine P1 receptor antagonist and by inhibitors of CD39 and CD73, which metabolize ATP to adenosine. These results suggest that adenosine is required for the ATP-induced upregulation of MHC-I and MHC-II. In the mixed leukocyte reaction assay, ATP-stimulated BMDCs activated CD4 and CD8T cells and induced interferon-gamma (IFN-gamma) production by these T cells. Collectively, these results suggest that high concentrations of extracellular ATP upregulate the expression of antigenpresenting and co-stimulatory molecules but not that of coinhibitory molecules in BMDCs. Cooperative stimulation of ATP and its metabolite adenosine was required for the upregulation of MHC-I and MHC-II. These ATP-stimulated BMDCs induced the activation of IFN-gamma-producing T cells upon antigen presentation.
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発行日 | 2023-04
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出版物タイトル |
Journal of Biological Chemistry
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巻 | 299巻
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号 | 4号
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出版者 | Elsevier
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開始ページ | 104587
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ISSN | 1083-351X
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資料タイプ |
学術雑誌論文
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言語 |
英語
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OAI-PMH Set |
岡山大学
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著作権者 | © 2023 THE AUTHORS.
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論文のバージョン | publisher
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PubMed ID | |
DOI | |
Web of Science KeyUT | |
関連URL | isVersionOf https://doi.org/10.1016/j.jbc.2023.104587
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ライセンス | http://creativecommons.org/licenses/by/4.0/
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助成機関名 |
Japan Society for the Promotion of Science
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助成番号 | 17K08273
20K07030
19K03466
22H02869
22K19435
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