The emerging roles of eosinophils in immune regulation in health and disease

Eosinophils are evolutionarily conserved granular innate cells that can trace back to 100 million years to the emergence of gnathostomes, which now is involved in regulation of diverse homeostatic conditions and diseases in mammals. They have traditionally been associated with Th2 responses, primarily in eosinophilic allergic asthma and helminth parasitic infections. These Th2 responses are correlated with basic cationic proteins and specific cytokines release from preformed eosinophilic vesicles, associated with tissue damage and remodeling. Consequently, eosinophils have historically been characterized as potent cytotoxic effector cells. In human patients, their high blood count has been linked to clinical concerns and necessary further patient evaluations. However, this reflects only a cursory understanding of eosinophils, as their involvement in a broad and diverse range of disorders has recently emerged. Indeed, eosinophils extend beyond traditionally ascribed Th2 responses, which appear to be both global and pivotal in immune regulation contexts. Its role varies from speculative controlled embryological tissue modeling, to tissue regeneration post-injury, uncontrolled neoplastic development, novel Th2 eosinophilic gastrointestinal disorders, reproductive homeostasis and SARS-CoV-2 in a non-exhaustive list of its emerging association with health and disease. This review evaluates the emerging roles of eosinophils which are both pro- and anti-inflammatory, dependent on disease context and microenvironment. Our knowledge of the novel and diverse roles of eosinophils has been applied to the emergence of targeted, and successful clinical therapies to a range of diseases, opening doors to extend assessment on their potential roles in the original embryological modeling and development. Collectively, diverse modern evidence indicates that eosinophils-an ancient evolutionarily conserved cell lineage-has an imperative function in immune networks.