Pyruvate–GPR31 axis induces LysoDC dendrite protrusion to M-cell pockets for effective immune responses
Peyer’s patches (PPs) are sites of antigen entry and immunoinduction in the small intestine. In PPs, pathogens are transferred through microfold (M) cells; however, the mechanisms of antigen capture by mononuclear phagocytes beneath M cells remain unclear. Here, we demonstrate that bacterial metabol...
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| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2025-12-01
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| Series: | Gut Microbes |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/19490976.2025.2536089 |
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| author | Katsuhiro Nakanishi Takayuki Ajiro Kaito Yukishima Yuki Tsukamoto Junichi Kikuta Shinichiro Sawa Michio Tomura Nozomi Kinoshita Wataru Shimanuki Akio Suzuki Shun Arai Kazuki Maeshima Takumi Ichisawa Tomoya Katakai Haruko Hayasaka Masaru Ishii Eiji Umemoto |
| author_facet | Katsuhiro Nakanishi Takayuki Ajiro Kaito Yukishima Yuki Tsukamoto Junichi Kikuta Shinichiro Sawa Michio Tomura Nozomi Kinoshita Wataru Shimanuki Akio Suzuki Shun Arai Kazuki Maeshima Takumi Ichisawa Tomoya Katakai Haruko Hayasaka Masaru Ishii Eiji Umemoto |
| author_sort | Katsuhiro Nakanishi |
| collection | DOAJ |
| description | Peyer’s patches (PPs) are sites of antigen entry and immunoinduction in the small intestine. In PPs, pathogens are transferred through microfold (M) cells; however, the mechanisms of antigen capture by mononuclear phagocytes beneath M cells remain unclear. Here, we demonstrate that bacterial metabolite pyruvate acted on lysozyme-expressing dendritic cells (LysoDCs), a monocyte-derived phagocyte subset, and induced protrusion of dendrites particularly with “balloon” shapes into basolateral M-cell pockets via its receptor, G-protein coupled receptor 31 (GPR31). Pyruvate administration in wild-type but not Gpr31b-deficient mice increased LysoDC uptake of orally infected Listeria monocytogenes. GPR31 signaling boosted antigen processing and altered gene expression. It also increased LysoDC migration to the interfollicular region, thereby promoting production of pathogen-specific Th1 cells as well as cytotoxic T cells, and effector T cell migration to the lamina propria. Furthermore, oral pyruvate administration conferred high resistance to a virulent L. monocytogenes strain in a GPR31-dependent manner. Collectively, the pyruvate – GPR31 axis plays critical roles in orchestrating intestinal protective immunity. |
| format | Article |
| id | doaj-art-e4f82073c9e64b48aaa6736705d07ec5 |
| institution | Kabale University |
| issn | 1949-0976 1949-0984 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Gut Microbes |
| spelling | doaj-art-e4f82073c9e64b48aaa6736705d07ec52025-08-20T04:02:22ZengTaylor & Francis GroupGut Microbes1949-09761949-09842025-12-0117110.1080/19490976.2025.2536089Pyruvate–GPR31 axis induces LysoDC dendrite protrusion to M-cell pockets for effective immune responsesKatsuhiro Nakanishi0Takayuki Ajiro1Kaito Yukishima2Yuki Tsukamoto3Junichi Kikuta4Shinichiro Sawa5Michio Tomura6Nozomi Kinoshita7Wataru Shimanuki8Akio Suzuki9Shun Arai10Kazuki Maeshima11Takumi Ichisawa12Tomoya Katakai13Haruko Hayasaka14Masaru Ishii15Eiji Umemoto16Laboratory of Microbiology and Immunology, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, JapanLaboratory of Microbiology and Immunology, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, JapanLaboratory of Microbiology and Immunology, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, JapanLaboratory of Microbiology and Immunology, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, JapanDivision of Immunology, Department of Future Medical Sciences, Graduate School of Medicine, Kobe University, Hyogo, JapanDivision of Mucosal Immunology, Research Center for Systems Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, JapanLaboratory of Immunology, Faculty of Pharmacy, Osaka Ohtani University, Osaka, JapanLaboratory of Microbiology and Immunology, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, JapanLaboratory of Microbiology and Immunology, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, JapanDivision of Immunology, Department of Future Medical Sciences, Graduate School of Medicine, Kobe University, Hyogo, JapanLaboratory of Microbiology and Immunology, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, JapanLaboratory of Microbiology and Immunology, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, JapanLaboratory of Microbiology and Immunology, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, JapanDepartment of Immunology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, JapanDepartment of Life Science, Faculty of Science & Engineering, Kindai University, Osaka, JapanDepartment of Immunology and Cell Biology, Graduate School of Medicine, Osaka University, Osaka, JapanLaboratory of Microbiology and Immunology, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, JapanPeyer’s patches (PPs) are sites of antigen entry and immunoinduction in the small intestine. In PPs, pathogens are transferred through microfold (M) cells; however, the mechanisms of antigen capture by mononuclear phagocytes beneath M cells remain unclear. Here, we demonstrate that bacterial metabolite pyruvate acted on lysozyme-expressing dendritic cells (LysoDCs), a monocyte-derived phagocyte subset, and induced protrusion of dendrites particularly with “balloon” shapes into basolateral M-cell pockets via its receptor, G-protein coupled receptor 31 (GPR31). Pyruvate administration in wild-type but not Gpr31b-deficient mice increased LysoDC uptake of orally infected Listeria monocytogenes. GPR31 signaling boosted antigen processing and altered gene expression. It also increased LysoDC migration to the interfollicular region, thereby promoting production of pathogen-specific Th1 cells as well as cytotoxic T cells, and effector T cell migration to the lamina propria. Furthermore, oral pyruvate administration conferred high resistance to a virulent L. monocytogenes strain in a GPR31-dependent manner. Collectively, the pyruvate – GPR31 axis plays critical roles in orchestrating intestinal protective immunity.https://www.tandfonline.com/doi/10.1080/19490976.2025.2536089Peyer’s patchcommensal metaboliteGPCR: dendritic cellListeria monocytogenes |
| spellingShingle | Katsuhiro Nakanishi Takayuki Ajiro Kaito Yukishima Yuki Tsukamoto Junichi Kikuta Shinichiro Sawa Michio Tomura Nozomi Kinoshita Wataru Shimanuki Akio Suzuki Shun Arai Kazuki Maeshima Takumi Ichisawa Tomoya Katakai Haruko Hayasaka Masaru Ishii Eiji Umemoto Pyruvate–GPR31 axis induces LysoDC dendrite protrusion to M-cell pockets for effective immune responses Gut Microbes Peyer’s patch commensal metabolite GPCR: dendritic cell Listeria monocytogenes |
| title | Pyruvate–GPR31 axis induces LysoDC dendrite protrusion to M-cell pockets for effective immune responses |
| title_full | Pyruvate–GPR31 axis induces LysoDC dendrite protrusion to M-cell pockets for effective immune responses |
| title_fullStr | Pyruvate–GPR31 axis induces LysoDC dendrite protrusion to M-cell pockets for effective immune responses |
| title_full_unstemmed | Pyruvate–GPR31 axis induces LysoDC dendrite protrusion to M-cell pockets for effective immune responses |
| title_short | Pyruvate–GPR31 axis induces LysoDC dendrite protrusion to M-cell pockets for effective immune responses |
| title_sort | pyruvate gpr31 axis induces lysodc dendrite protrusion to m cell pockets for effective immune responses |
| topic | Peyer’s patch commensal metabolite GPCR: dendritic cell Listeria monocytogenes |
| url | https://www.tandfonline.com/doi/10.1080/19490976.2025.2536089 |
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