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

Eosinophils are potent sources of inflammatory and toxic mediators, yet they reside in large numbers in the healthy intestine without causing tissue damage. We show here that intestinal eosinophils were specifically adapted to their environment and underwent substantial transcriptomic changes. Intestinal eosinophils upregulated genes relating to the immune response, cell-cell communication, extracellular matrix remodeling, and the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor with broad functions in intestinal homeostasis. Eosinophils from AHR-deficient mice failed to fully express the intestinal gene expression program, including extracellular matrix organization and cell junction pathways. AHR-deficient eosinophils were functionally impaired in the adhesion to and degradation of extracellular matrix, were more prone to degranulation, and had an extended life span. Lack of AHR in eosinophils had wider effects on the intestinal immune system, affecting the T cell compartment in nave and helminth-infected mice. Our study demonstrates that the response to environmental triggers via AHR partially shapes tissue adaptation of eosinophils in the small intestine. Eosinophils undergo tissue adaptation in the small intestine. Aryl hydrocarbon receptor-deficient eosinophils fail to induce the full intestinal gene expression program, are functionally impaired in extracellular matrix interactions, are more prone to degranulation, and have an extended life span.

Automated summary

Intestinal eosinophils undergo substantial transcriptomic changes and adapt to their environment through the aryl hydrocarbon receptor (AHR). AHR-deficient eosinophils exhibit impairments in function and interactions within the intestine.