Shaping eosinophil identity in the tissue contexts of development, homeostasis, and disease

Abstract

Eosinophils play homeostatic roles in different tissues and are found in several organs at a homeostatic baseline, though their tissue numbers increase significantly in development and disease. The morphological, phenotypical, and functional plasticity of recruited eosinophils are influenced by the dynamic tissue microenvironment changes between homeostatic, morphogenetic, and disease states. Activity of the epithelial-mesenchymal interface, extracellular matrix, hormonal inputs, metabolic state of the environment, as well as epithelial and mesenchymal-derived innate cytokines and growth factors all have the potential to regulate the attraction, retention, in situ hematopoiesis, phenotype, and function of eosinophils. This review examines the reciprocal relationship between eosinophils and such tissue factors, specifically addressing: (1) tissue microenvironments associated with the presence and activity of eosinophils; (2) non-immune tissue ligands regulatory for eosinophil accumulation, hematopoiesis, phenotype, and function (with an emphasis on the extracellular matrix and epithelial-mesenchymal interface); (3) the contribution of eosinophils to regulating tissue biology; (4) eosinophil phenotypic heterogeneity in different tissue microenvironments, classifying eosinophils as progenitors, steady state eosinophils, and Type 1 and 2 activated phenotypes. An appreciation of eosinophil regulation by non-immune tissue factors is necessary for completing the picture of eosinophil immune activation and understanding the functional contribution of these cells to development, homeostasis, and disease.

Deciphering the role of eosinophils in solid organ transplantation

“…Despite their established role in cytotoxicity, we, as well as others, have previously proposed that eosinophils have the capacity for broad dynamic differential activation and may vary their function drastically based on environmental cues. 9,41 The mechanisms of immune suppression by eosinophils that have been identified primarily in animal models are through either release of suppressive molecules and/or cell interactions with dendritic cells and lymphocytes. A homeostatic mechanism of immune suppression has been identified for tissue-resident eosinophils in the lung that exhibit suppressive capacity to allergen-induced Th2 immune responses.…”

Frontline Science: Cytokine-mediated developmental phenotype of mouse eosinophils: IL-5-associated expression of the Ly6G/Gr1 surface Ag

“…While much of the older literature on eosinophils focuses on their role as cytotoxic effector cells, this limited view has been largely supplanted by findings that have revealed their broad and extensive immunomodulatory potential . Recent studies that explore the role of eosinophils at homeostasis in the gastrointestinal tract, that examine their distinct eosinophil‐mediated antimicrobial activities and that define the properties of eosinophil‐specific subtypes, all suggest that there are new and profound complexities remaining to be resolved.…”

Revisiting the NIH Taskforce on the Research needs of Eosinophil-Associated Diseases (RE-TREAD)

“…]. Despite this progress, there is still much to learn regarding the interaction of eosinophils and their response to tissue components, such as matrix proteins, fibroblasts, epithelium, and other tissue‐resident cells . It is known that the engagement and expression of integrins can engage matrix proteins, such as fibronectin and laminin, and that these interactions alter eosinophil biology including degranulation and survival .…”