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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.
摘要：
Peyer's斑块中的肠微折细胞（M细胞）是上皮细胞的特殊子集，通过吸收腔抗原启动粘膜免疫反应。尽管在间充质细胞上表达的核因子-κB配体（RANKL）的细胞因子受体激活剂触发分化为M细胞，其他环境线索仍然未知。这里,我们表明，转移促进蛋白S100A4是成熟M细胞发育所必需的。产生S100A4的细胞是异源细胞群,包括表达溶菌酶的树突状细胞和第3组先天淋巴样细胞。我们发现，在没有DOCK8的情况下，Cdc42激活剂对间质白细胞迁移至关重要，产生S100A4的细胞在上皮下圆顶中减少，导致M细胞的成熟缺陷。虽然S100A4在类器官培养中促进分化为成熟M细胞，S100a4的遗传失活阻止了小鼠成熟M细胞的发育。因此，S100A4是与RANKL合作调节M细胞分化的关键环境线索。
