S100A4 Protein Is Essential for the Development of Mature Microfold Cells in Peyer’s Patches
| Autor: | Takehito Uruno, Miho Ushijima, Ryosuke Aihara, Shouichi Ohga, Yasunobu Yoshikai, Yasuhisa Kamikaseda, Shinichiro Sawa, Daiji Sakata, Keisuke Matsubara, Tomoya Katakai, Hirokazu Kanegane, Xin Tun, Yoshinori Fukui, Akira Shiraishi, Kazufumi Kunimura, Gérard Eberl |
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| Přispěvatelé: | Kyushu University, Niigata University, Tokyo Medical and Dental University [Japan] (TMDU), Microenvironnement et Immunité - Microenvironment and Immunity, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), This research was supported by the Leading Advanced Projects for Medical Innovation (LEAP JP19gm0010001 to Y.F.), Core Research for Evolutionary Medical Science and Technology (CREST JP19gm1310005 to Y.F.), and the Practical Research Project for Allergic Diseases and Immunology (JP19ek0410064 to Y.F.) from the Japan Agency for Medical Research and Development (AMED)., Kyushu University [Fukuoka], Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), HUGOT, Bérengère |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
MESH: Cell Differentiation
Leukocyte migration [SDV]Life Sciences [q-bio] Population intestinal immunity General Biochemistry Genetics and Molecular Biology Peyer's Patches 03 medical and health sciences 0302 clinical medicine Antigen MESH: S100 Calcium-Binding Protein A4 medicine Humans S100 Calcium-Binding Protein A4 Lymphocytes education Peyer's patch S100A4-producing cells lcsh:QH301-705.5 030304 developmental biology Microfold cell 0303 health sciences education.field_of_study MESH: Humans biology Mesenchymal stem cell Innate lymphoid cell Cell Differentiation M cell maturation DOCK8 Cell biology [SDV] Life Sciences [q-bio] medicine.anatomical_structure lcsh:Biology (General) RANKL biology.protein MESH: Peyer's Patches MESH: Lymphocytes 030215 immunology |
| Zdroj: | Cell Reports Cell Reports, 2019, 29 (9), pp.2823-2834.e7. ⟨10.1016/j.celrep.2019.10.091⟩ Cell Reports, Elsevier Inc, 2019, 29 (9), pp.2823-2834.e7. ⟨10.1016/j.celrep.2019.10.091⟩ Cell Reports, Vol 29, Iss 9, Pp 2823-2834.e7 (2019) |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2019.10.091⟩ |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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