Eosinophils promote a second wave of postnatal smooth muscle differentiation in intestinal villi.

Intestinal villus smooth muscle cells (SMCs) play a critical structural and functional role in the gut, notably facilitating dietary fat transport via villus-associated lymphatic lacteals. In the early postnatal period, subepithelial PDGFRα+ fibroblasts are guided by lacteals to differentiate and assemble into villus SMCs. We show now that villus SMC expansion can occur in the absence of lacteals, suggesting the involvement of additional mechanisms. Using whole-mount imaging, genetic lineage tracing, and eosinophil-deficient models, we identify a second wave of intestinal SMC differentiation where villus tip perivascular PDGFRβ+ cells are a reservoir of distal SMC progenitors. We demonstrate that resident intestinal eosinophils act as key drivers and coordinators of TGFβ-dependent villus SMC expansion and maturation. Our findings propose a model in which PDGFRβ+ perivascular cells are progenitors for a second wave of postnatal villus SMCs and reveal a novel morphogenetic role of intestinal eosinophils as critical mediators of SMC development in the gut.