# KIT supports small intestinal tuft cell hyperplasia

## TL;DR

The KIT receptor helps tuft cells in the small intestine multiply during infections, aiding in clearing parasites.

## Contribution

This study identifies KIT as a novel driver of tuft cell hyperplasia during type 2 immune responses in the small intestine.

## Key findings

- KIT is up-regulated on small intestinal tuft cells during type 2 inflammation.
- KIT signaling supports new tuft cell generation in intestinal crypts during helminth infection.
- KIT deletion in tuft cells reduces hyperplasia and delays helminth clearance.

## 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.

Small intestinal type 2 inflammation up-regulates KIT on tuft cells to promote tuft cell hyperplasia and helminth clearance.