S100A4 Protein Is Essential for the Development of Mature Microfold Cells in Peyer’s Patches.<\/p>\n\n\n\n
Kunimura K<\/strong>, Sakata D<\/strong>, Tun X, Uruno T<\/strong>, Ushijima M<\/strong>, Katakai T, Shiraishi A<\/strong>, Aihara R<\/strong>, Kamikaseda Y<\/strong>, Matsubara K<\/strong>, Kanegane H, Sawa S, Eberl G, Ohga S, Yoshikai Y, Fukui Y<\/strong>:<\/p>\n\n\n\n Cell Reports<\/strong> 29(9): 2823-2834, 2019<\/strong>. <\/p>\n\n\n\n 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-\u03baB 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.<\/p>\n\n\n\n