Authors: Marija S. Nadjsombati, Natalie Niepoth, Lily M. Webeck, Elizabeth A. Kennedy, Danielle L. Jones, Tyler E. Billipp, Megan T. Baldridge, Andres Bendesky, Jakob von Moltke
Published: 2023-05-12
DOI: 10.1126/sciimmunol.ade5019
Source: Full article
Chemosensory epithelial tuft cells contribute to innate immunity at barrier surfaces, but their differentiation from epithelial progenitors is not well understood. Here, we exploited differences between inbred mouse strains to identify an epithelium-intrinsic mechanism that regulates tuft cell differentiation and tunes innate type 2 immunity in the small intestine. Balb/cJ (Balb) mice had fewer intestinal tuft cells than C57BL/6J (B6) mice and failed to respond to the tuft cell ligand succinate. Most of this differential succinate response was determined by the 50- to 67-Mb interval of chromosome 9 (Chr9), such that congenic Balb mice carrying the B6 Chr9 interval had elevated baseline numbers of tuft cells and responded to succinate. The Chr9 locus includes