{Reference Type}: Journal Article
{Title}: S100A4 Protein Is Essential for the Development of Mature Microfold Cells in Peyer's Patches.
{Author}: 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;
{Journal}: Cell Rep
{Volume}: 29
{Issue}: 9
{Year}: 11 2019 26
暂无{DOI}: 10.1016/j.celrep.2019.10.091
{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.