Single-cell RNA sequencing unveils intestinal eosinophil development and specialization

Abstract

Eosinophils are an integral part of the gastrointestinal (GI) immune system that contribute to homeostatic and inflammatory processes. Here, we investigated the existence of functional subsets that carry out specialized tasks in health and disease. We used single-cell transcriptomics and high-dimensional flow cytometry to delineate murine eosinophil subpopulations and their ontogenetic relationship in the steady state and during infection and inflammation. Profiling of eosinophils from bone marrow, blood, spleen and several GI tissues revealed five distinct subsets representing consecutive developmental and maturation stages across organs, each controlled by a specific set of transcription factors. Furthermore, we discovered a highly adapted PD-L1+CD80+ eosinophil subset in the GI tract, characterized by its immune regulatory properties, bactericidal activity upon challenge infection and tissue-protective function during inflammation. Our data provide a framework for the characterization of eosinophil subsets in GI diseases and highlight their crucial contribution to homeostasis, immune regulation and host defense.

Small intestinal resident eosinophils maintain gut homeostasis following microbial colonization

“…These markers are associated with eosinophil activation in response to intestinal inflammation (Arnold et al, 2018;Griseri et al, 2015), indicating that microbial colonization regulates the activation and/or maturation of intestinal eosinophils. Single-cell RNA-seq of murine eosinophils also indicated that eosinophil maturation in the gut is driven by microbiota-derived signals (Gurtner et al, 2021). Taken together, our results show that eosinophils respond to microbial colonization and play a critical role in facilitating homeostatic host-microbiota crosstalk by maintaining barrier integrity and regulating microbiota-dependent changes in intestinal physiology.…”

The aryl hydrocarbon receptor contributes to tissue adaptation of intestinal eosinophils in mice

“…This suggests that AHR-deficient eosinophils have a diminished ability to promote regulatory T cell differentiation. A previous study found that eosinophils suppress Th1 cells through PD-L1 (CD274; Arnold et al, 2018 ), and a recent preprint paper described a subset of CD80 + CD274 + eosinophils with high Ahr expression ( Gurtner et al, 2021 Preprint ). We found that this CD80 + CD724 + eosinophil subset was not affected by AHR deficiency ( Fig.…”

Hypereosinophilia causes progressive cardiac pathologies in mice

“…Compared to WT eosinophils, those from IL-5Tg hearts expressed lower levels of CD101 and CD62L, a marker of tissue-resident lung eosinophils that is reduced in inflammatory eosinophils 29 ( Figures 5 E and 5F). PDL1 expression, shown to increase after bacterial infection, 30 was higher in IL-5Tg eosinophils ( Figure 5 G). Overall, this shows that cardiac eosinophils from IL-5Tg mice display an activated phenotype.…”