S100A4 Protein Is Essential for the Development of Mature Microfold Cells in Peyer's Patches

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

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Abstract

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.

Original languageEnglish
Pages (from-to)2823-2834.e7
JournalCell Reports
Volume29
Issue number9
DOIs
Publication statusPublished - Nov 26 2019

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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    Kunimura, K., Sakata, D., Tun, X., Uruno, T., Ushijima, M., Katakai, T., Shiraishi, A., Aihara, R., Kamikaseda, Y., Matsubara, K., Kanegane, H., Sawa, S., Eberl, G., Ohga, S., Yoshikai, Y., & Fukui, Y. (2019). S100A4 Protein Is Essential for the Development of Mature Microfold Cells in Peyer's Patches. Cell Reports, 29(9), 2823-2834.e7. https://doi.org/10.1016/j.celrep.2019.10.091