Epithelial–stromal interaction via N otch signaling is essential for the full maturation of gut‐associated lymphoid tissues

Abstract

Intrinsic Notch signaling in intestinal epithelial cells restricts secretory cell differentiation. In gut‐associated lymphoid tissue ( GALT ), stromal cells located beneath the follicle‐associated epithelium ( FAE ) abundantly express the Notch ligand delta‐like 1 (Dll1). Here, we show that mice lacking Rbpj —a gene encoding a transcription factor implicated in Notch signaling—in intestinal epithelial cells have defective GALT maturation. This defect can be attributed to the expansion of goblet cells, which leads to the down‐regulation of CCL 20 in FAE . These data demonstrate that epithelial Notch signaling maintained by stromal cells contributes to the full maturation of GALT by restricting secretory cell differentiation in FAE . image The stromal cells located beneath the follicle‐associated epithelium ( FAE ) that covers Peyer's patches express Notch ligand. The induction of Notch signaling in FAE is shown to ensure lymphoid follicle compartmentalization in gut‐associated lymphoid tissues by restricting secretory cell differentiation. This is the first report that demonstrates the contribution of intestinal epithelial cells to the GALT organogenesis. Notch signaling regulates FAE cellular composition. Mice lacking epithelial Notch signaling have defects in GALT maturation and antigen‐specific mucosal immune responses.