%0 Journal Article
%T S100A4 Protein Is Essential for the Development of Mature Microfold Cells in Peyer's Patches.
%A Kunimura K
%A Sakata D
%A Tun X
%A Uruno T
%A Ushijima M
%A Katakai T
%A Shiraishi A
%A Aihara R
%A Kamikaseda Y
%A Matsubara K
%A Kanegane H
%A Sawa S
%A Eberl G
%A Ohga S
%A Yoshikai Y
%A Fukui Y
%J Cell Rep
%V 29
%N 9
%D 11 2019 26
%M 31775048
暂无%R 10.1016/j.celrep.2019.10.091
%X 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.