KIT supports small intestinal tuft cell hyperplasia.

Abstract

The small intestine balances the competing tasks of nutrient absorption, immune tolerance, and defense through dynamic differentiation of short-lived epithelial cells. During helminth infection, interleukin-13 (IL-13) or IL-4 drive a 10-fold expansion of tuft cells to promote helminth clearance. While IL-4/13 signaling in epithelial cells is required for tuft cell hyperplasia, few signals that support this process have been identified. Here, we show that tuft cells across all tissues express the receptor tyrosine kinase KIT and that IL-4/13 is necessary and sufficient to up-regulate KIT on small intestinal (SI) tuft cells. Although epithelial KIT is dispensable for homeostatic turnover, KIT deletion from tuft cells during helminth infection reduces tuft cell hyperplasia and delays helminth clearance. Mechanistically, KIT signaling supports the generation of new tuft cells in SI crypts. These findings thus identify a unique tuft cell-specific function for KIT in type 2 immunity.