| First Author | Kunimura K | Year | 2019 |
| Journal | Cell Rep | Volume | 29 |
| Issue | 9 | Pages | 2823-2834.e7 |
| PubMed ID | 31775048 | Mgi Jnum | J:299945 |
| Mgi Id | MGI:6488903 | Doi | 10.1016/j.celrep.2019.10.091 |
| Citation | Kunimura K, et al. (2019) S100A4 Protein Is Essential for the Development of Mature Microfold Cells in Peyer's Patches. Cell Rep 29(9):2823-2834.e7 |
| abstractText | 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-kappaB 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. |
