S100A4 Protein Is Essential for the Development of Mature Microfold Cells in Peyer’s Patches
Summary: Intestinal microfold cells (M cells) in Peyer’s patches are a special subset of epithelial cells that initiate mucosal immune responses through uptake of luminal antigens. Although the cytokine receptor activator of nuclear factor-κB ligand (RANKL) expressed on mesenchymal cells triggers di...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2019-11-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124719314135 |
| _version_ | 1828776641675919360 |
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| author | Kazufumi Kunimura Daiji Sakata Xin Tun Takehito Uruno Miho Ushijima Tomoya Katakai Akira Shiraishi Ryosuke Aihara Yasuhisa Kamikaseda Keisuke Matsubara Hirokazu Kanegane Shinichiro Sawa Gérard Eberl Shouichi Ohga Yasunobu Yoshikai Yoshinori Fukui |
| author_facet | Kazufumi Kunimura Daiji Sakata Xin Tun Takehito Uruno Miho Ushijima Tomoya Katakai Akira Shiraishi Ryosuke Aihara Yasuhisa Kamikaseda Keisuke Matsubara Hirokazu Kanegane Shinichiro Sawa Gérard Eberl Shouichi Ohga Yasunobu Yoshikai Yoshinori Fukui |
| author_sort | Kazufumi Kunimura |
| collection | DOAJ |
| description | Summary: Intestinal microfold cells (M cells) in Peyer’s patches are a special subset of epithelial cells that initiate mucosal immune responses through uptake of luminal antigens. Although the cytokine receptor activator of nuclear factor-κB ligand (RANKL) expressed on mesenchymal cells triggers differentiation into M cells, other environmental cues remain unknown. Here, we show that the metastasis-promoting protein S100A4 is required for development of mature M cells. S100A4-producing cells are a heterogenous cell population including lysozyme-expressing dendritic cells and group 3 innate lymphoid cells. We found that in the absence of DOCK8, a Cdc42 activator critical for interstitial leukocyte migration, S100A4-producing cells are reduced in the subepithelial dome, resulting in a maturation defect of M cells. While S100A4 promotes differentiation into mature M cells in organoid culture, genetic inactivation of S100a4 prevents the development of mature M cells in mice. Thus, S100A4 is a key environmental cue that regulates M cell differentiation in collaboration with RANKL. : Kunimura et al. find that in the absence of DOCK8, S100A4-producing cells are reduced in the subepithelial dome, resulting in a maturation defect of M cells in Peyer’s patches. In vitro and in vivo studies demonstrate that S100A4 protein is a key environmental factor that promotes M cell maturation. Keywords: intestinal immunity, Peyer's patch, M cell maturation, DOCK8, S100A4-producing cells |
| first_indexed | 2024-12-11T16:03:20Z |
| format | Article |
| id | doaj.art-fc980c95664743ec9b9d7d107be4329d |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-11T16:03:20Z |
| publishDate | 2019-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-fc980c95664743ec9b9d7d107be4329d2022-12-22T00:59:16ZengElsevierCell Reports2211-12472019-11-0129928232834.e7S100A4 Protein Is Essential for the Development of Mature Microfold Cells in Peyer’s PatchesKazufumi Kunimura0Daiji Sakata1Xin Tun2Takehito Uruno3Miho Ushijima4Tomoya Katakai5Akira Shiraishi6Ryosuke Aihara7Yasuhisa Kamikaseda8Keisuke Matsubara9Hirokazu Kanegane10Shinichiro Sawa11Gérard Eberl12Shouichi Ohga13Yasunobu Yoshikai14Yoshinori Fukui15Division of Immunogenetics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, JapanDivision of Immunogenetics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan; Research Center for Advanced Immunology, Kyushu University, Fukuoka 812-8582, JapanDivision of Host Defence, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, JapanDivision of Immunogenetics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan; Research Center for Advanced Immunology, Kyushu University, Fukuoka 812-8582, JapanDivision of Immunogenetics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, JapanDepartment of Immunology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, JapanDepartment of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, JapanDivision of Immunogenetics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, JapanDivision of Immunogenetics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, JapanDivision of Immunogenetics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, JapanDepartment of Child Health and Development, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8519, JapanDivision of Mucosal Immunology, Research Center for Systems Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, JapanMicroenvironment & Immunity Unit, INSERM U1224, Institut Pasteur, Paris 75724, FranceDepartment of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, JapanDivision of Host Defence, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, JapanDivision of Immunogenetics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan; Research Center for Advanced Immunology, Kyushu University, Fukuoka 812-8582, Japan; Corresponding authorSummary: Intestinal microfold cells (M cells) in Peyer’s patches are a special subset of epithelial cells that initiate mucosal immune responses through uptake of luminal antigens. Although the cytokine receptor activator of nuclear factor-κB ligand (RANKL) expressed on mesenchymal cells triggers differentiation into M cells, other environmental cues remain unknown. Here, we show that the metastasis-promoting protein S100A4 is required for development of mature M cells. S100A4-producing cells are a heterogenous cell population including lysozyme-expressing dendritic cells and group 3 innate lymphoid cells. We found that in the absence of DOCK8, a Cdc42 activator critical for interstitial leukocyte migration, S100A4-producing cells are reduced in the subepithelial dome, resulting in a maturation defect of M cells. While S100A4 promotes differentiation into mature M cells in organoid culture, genetic inactivation of S100a4 prevents the development of mature M cells in mice. Thus, S100A4 is a key environmental cue that regulates M cell differentiation in collaboration with RANKL. : Kunimura et al. find that in the absence of DOCK8, S100A4-producing cells are reduced in the subepithelial dome, resulting in a maturation defect of M cells in Peyer’s patches. In vitro and in vivo studies demonstrate that S100A4 protein is a key environmental factor that promotes M cell maturation. Keywords: intestinal immunity, Peyer's patch, M cell maturation, DOCK8, S100A4-producing cellshttp://www.sciencedirect.com/science/article/pii/S2211124719314135 |
| spellingShingle | Kazufumi Kunimura Daiji Sakata Xin Tun Takehito Uruno Miho Ushijima Tomoya Katakai Akira Shiraishi Ryosuke Aihara Yasuhisa Kamikaseda Keisuke Matsubara Hirokazu Kanegane Shinichiro Sawa Gérard Eberl Shouichi Ohga Yasunobu Yoshikai Yoshinori Fukui S100A4 Protein Is Essential for the Development of Mature Microfold Cells in Peyer’s Patches Cell Reports |
| title | S100A4 Protein Is Essential for the Development of Mature Microfold Cells in Peyer’s Patches |
| title_full | S100A4 Protein Is Essential for the Development of Mature Microfold Cells in Peyer’s Patches |
| title_fullStr | S100A4 Protein Is Essential for the Development of Mature Microfold Cells in Peyer’s Patches |
| title_full_unstemmed | S100A4 Protein Is Essential for the Development of Mature Microfold Cells in Peyer’s Patches |
| title_short | S100A4 Protein Is Essential for the Development of Mature Microfold Cells in Peyer’s Patches |
| title_sort | s100a4 protein is essential for the development of mature microfold cells in peyer s patches |
| url | http://www.sciencedirect.com/science/article/pii/S2211124719314135 |
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