Eosinophils in Health and Disease: A State-of-the-Art Review

Abstract

Eosinophils play a homeostatic role in the body's immune responses. These cells are involved in combating some parasitic, bacterial, and viral infections and certain cancers and have pathologic roles in diseases including asthma, chronic rhinosinusitis with nasal polyps, eosinophilic gastrointestinal disorders, and hypereosinophilic syndromes. Treatment of eosinophilic diseases has traditionally been through nonspecific eosinophil attenuation by use of glucocorticoids. However, several novel biologic therapies targeting eosinophil maturation factors, such as interleukin (IL)-5 and the IL-5 receptor or IL-4/IL-13, have recently been approved for clinical use. Despite the success of biologic therapies, some patients with eosinophilic inflammatory disease may not achieve adequate symptom control, underlining the need to further investigate the contribution of patient characteristics, such as comorbidities and other processes, in driving ongoing disease activity. New research has shown that eosinophils are also involved in several homeostatic processes, including metabolism, tissue remodeling and development, neuronal regulation, epithelial and microbiome regulation, and immunoregulation, indicating that these cells may play a crucial role in metabolic regulation and organ function in healthy humans. Consequently, further investigation is needed into the homeostatic roles of eosinophils and eosinophil-mediated processes across different tissues and their varied microenvironments. Such work may provide important insights into the role of eosinophils not only under disease conditions but also in health. This narrative review synthesizes relevant publications retrieved from PubMed informed by author expertise to provide new insights into the diverse roles of eosinophils in health and disease, with particular emphasis on the implications for current and future development of eosinophil-targeted therapies.

Immune Activation in Functional Dyspepsia: Bystander Becoming the Suspect

“…Eosinophil activation results in degranulation with release of various cytotoxic granular proteins including major basic protein (MBP), eosinophil cationic protein (ECP), eosinophil peroxidase (EPO) and eosinophil-derived neurotoxin (EDN) ( Rothenberg and Hogan, 2006 ). However, recent findings increasingly point toward an important contribution of eosinophils to GI homeostasis ( Shah et al, 2020 ; Masterson et al, 2021 ; Wechsler et al, 2021 ). These novel roles include promoting the survival and class switching of immunoglobulin (Ig)A-producing plasma cells, supporting IL-1β-mediated IgA production, maintaining Th17 cell differentiation and supporting microbial homeostasis, mucus production and inflammatory homeostasis in the intestinal microenvironment ( Jung et al, 2015 ; Marichal et al, 2017 ).…”

Elevated eosinophils as predictor of immune-related adverse events after ipilimumab and nivolumab treatment of advanced and metastatic renal cell carcinoma

“…They combat several parasitic, bacterial, and viral infections by interacting with B cells, T cells, macrophages, and neutrophils. Eosinophils are further involved in the regulation of several diseases, including allergic asthma, esophagitis, myopathies, and autoimmune disorders due to directly or indirectly promoting tissue damage or altering the local immune status [14][15][16] . A recent study showed that upregulation of the eosinophil count in the peripheral blood is linked with a better prognosis and response to ICI therapy.…”

Eosinophils in the Gastrointestinal Tract: Key Contributors to Neuro-Immune Crosstalk and Potential Implications in Disorders of Brain-Gut Interaction

“…Consequently, resident and newly recruited eosinophils may respond to specific tissue requirements. This response implicates the regulation of immunoglobulin production, the promotion of both anti-and pro-inflammatory networks, tissue remodeling and repair, and modulation of epithelial barrier function at mucosal sites [6][7][8]. Notably, the gastrointestinal tract harbors the largest number of resident eosinophils in the body and eosinophilia and eosinophil activation are associated with gut dysfunction in a variety of inflammatory diseases, such as eosinophilic gastrointestinal diseases (EGIDs) and inflammatory bowel disease (IBD), and in other non-inflammatory entities, such as the disorders of brain-gut interaction (DBGIs).…”