Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 21, 2019; 25(27): 3503-3526
Published online Jul 21, 2019. doi: 10.3748/wjg.v25.i27.3503
Eosinophils in the gastrointestinal tract and their role in the pathogenesis of major colorectal disorders
Alexandre Loktionov
Alexandre Loktionov, DiagNodus Ltd, Babraham Research Campus, Cambridge CB22 3AT, United Kingdom
Author contributions: Loktionov A is responsible for all work related to the preparation of this review. He has designed paper structure, performed literature search, contributed figures, analysed literature data and wrote the paper.
Conflict-of-interest statement: No potential conflicts of interest. No financial support.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Alexandre Loktionov, MD, PhD, Director, DiagNodus Ltd, Bldg 280, Babraham Research Campus, Cambridge CB22 3AT, United Kingdom.
Telephone: +44-1223-497181
Received: March 6, 2019
Peer-review started: March 6, 2019
First decision: May 16, 2019
Revised: May 22, 2019
Accepted: May 31, 2019
Article in press: June 1, 2019
Published online: July 21, 2019

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.