Functions of tissue-resident eosinophils

Key Points Eosinophils, as cells of the innate immune system and sources of diverse cytokines, function in diverse tissue sites, some previously unappreciated, in health and disease. At least in human eosinophils, many cytokine proteins are present preformed and stored within eosinophil cytoplasmic granules. Eosinophil secretion of cytokines can occur by regulated transport of granule-derived proteins through the vesicular transport system to enable extracellular release. The relative contributions to eosinophil cytokine secretion of preformed granule stores, de novo transcription and mRNA transcript stabilization remain to be determined. The signalling mechanisms within eosinophils that regulate the selective secretion of specific cytokines remain to be elucidated. Eosinophil-secreted cytokines can contribute to immune and metabolic homeostasis, as well as having roles in tissue regeneration, wound healing and host defence. Tissue-resident eosinophils selectively secrete cytokines and other mediators that have diverse functions in health and disease. Eosinophils are a prominent cell type in particular host responses such as the response to helminth infection and allergic disease. Their effector functions have been attributed to their capacity to release cationic proteins stored in cytoplasmic granules by degranulation. However, eosinophils are now being recognized for more varied functions in previously underappreciated diverse tissue sites, based on the ability of eosinophils to release cytokines (often preformed) that mediate a broad range of activities into the local environment. In this Review, we consider evolving insights into the tissue distribution of eosinophils and their functional immunobiology, which enable eosinophils to secrete in a selective manner cytokines and other mediators that have diverse, 'non-effector' functions in health and disease.