Eosinophils in the gastrointestinal tract and their role in the pathogenesis of major colorectal disorders

Abstract

Eosinophils are currently regarded as versatile mobile cells controlling and regulating multiple biological pathways and responses in health and disease. These cells store in their specific granules numerous biologically active substances (cytotoxic cationic proteins, cytokines, growth factors, chemokines, enzymes) ready for rapid release. The human gut is the main destination of eosinophils that are produced and matured in the bone marrow and then transferred to target tissues through the circulation. In health the most important functions of gut-residing eosinophils comprise their participation in the maintenance of the protective mucosal barrier and interactions with other immune cells in providing immunity to microbiota of the gut lumen. Eosinophils are closely involved in the development of inflammatory bowel disease (IBD), when their cytotoxic granule proteins cause damage to host tissues. However, their roles in Crohn’s disease and ulcerative colitis appear to follow different immune response patterns. Eosinophils in IBD are especially important in altering the structure and protective functions of the mucosal barrier and modulating massive neutrophil influx to the lamina propria followed by transepithelial migration to colorectal mucus. IBD-associated inflammatory process involving eosinophils then appears to expand to the mucus overlaying the internal gut surface. The author hypothesises that immune responses within colorectal mucus as well as ETosis exerted by both neutrophils and eosinophils on the both sides of the colonic epithelial barrier act as additional pathogenetic factors in IBD. Literature analysis also shows an association between elevated eosinophil levels and better colorectal cancer (CRC) prognosis, but mechanisms behind this effect remain to be elucidated. In conclusion, the author emphasises the importance of investigating colorectal mucus in IBD and CRC patients as a previously unexplored milieu of disease-related inflammatory responses.

Keywords: Eosinophils, Eosinophilopoiesis, Gut lamina propria, Colorectal mucus, Normal human small intestine, Normal human colon, Inflammatory bowel disease, Crohn’s disease, Ulcerative colitis, Colorectal cancer

Core tip: Eosinophils are multifunctional granulocytes possessing readily releasable stores of cytotoxic proteins, regulatory cytokines and chemokines in their specific granules. In health eosinophils reside in the gut, exerting homeostatic functions including protective mucosal barrier integrity maintenance and contribution to gut-associated immunity. Eosinophils are important players in inflammatory bowel disease pathogenesis (both Crohn’s disease and ulcerative colitis). These cells are also associated with a favourable prognosis in colorectal cancer, however mechanisms of this association remain obscure. The author presents a comprehensive analysis of the current literature on eosinophils in the gut and highlights the importance of poorly investigated immune responses occurring within colorectal mucus.