Clec4a4+ and Clec4a4- eosinophils in the small intestine

Eosinophils contribute to parasitic helminths- and allergens-induced type 2 immune responses. Although the gastrointestinal tract harbors a substantial number of eosinophils, the pathophysiological roles of intestinal eosinophils remain unclear. Here we identify a novel subset of eosinophil that expresses a repertoire of inhibitory molecules, including Clec4a4 and PD-L1. These Clec4a4+ leukocytes are blood-derived and exclusively present in the small intestine. Accordingly, this subset acquires imprinted features by the instruction of AHR signaling, which modulates immune responses to establish gut homeostasis. Selective depletion of AHR in eosinophils leads to a marked reduction of Clec4a4+PD-L1+ eosinophils and enhances the worm clearance accompanied by an increased type 2 immune response. Our findings may open new therapeutic avenues on primary eosinophilic gastrointestinal disorders. 1. Profile the gene expression in sorted mCherry+ and mCherry- eosinophils from Clec4a4-mCherry reporter mice. 2. Profile the gene expression from sorted A. WT Clec4a4+ eosinophils, B. WT Clec4a4- eosinophils, and C. Ahr KO Clec4a4- eosinophils.