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

Abstract

Eosinophils are innate immune granulocytes actively involved in defensive responses and in local and systemic inflammatory processes. Beyond these effector roles, eosinophils are fundamental to maintaining homeostasis in the tissues they reside. Gastrointestinal eosinophils modulate barrier function and mucosal immunity and promote tissue development through their direct communication with almost every cellular component. This is possible thanks to the variety of receptors they express and the bioactive molecules they store and release, including cytotoxic proteins, cytokines, growth factors, and neuropeptides and neurotrophines. A growing body of evidence points to the eosinophil as a key neuro-immune player in the regulation of gastrointestinal function, with potential implications in pathophysiological processes. Eosinophil–neuron interactions are facilitated by chemotaxis and adhesion molecules, and the mediators released may have excitatory or inhibitory effects on each cell type, with physiological consequences dependent on the type of innervation involved. Of special interest are the disorders of the brain–gut interaction (DBGIs), mainly functional dyspepsia (FD) and irritable bowel syndrome (IBS), in which mucosal eosinophilia and eosinophil activation have been identified. In this review, we summarize the main roles of gastrointestinal eosinophils in supporting gut homeostasis and the evidence available on eosinophil–neuron interactions to bring new insights that support the fundamental role of this neuro-immune crosstalk in maintaining gut health and contributing to the pathophysiology of DBGIs.

Increased mucosal eosinophils in colonic diverticulosis and diverticular disease

“…Previous research on eosinophils has identified different roles and functions for resident (rEos) and induced (iEos) tissue eosinophils 18 . Intestinal rEos can be distinguished from iEos by their surface receptor expression (intermediate Siglec‐8 levels, a high cluster of differentiation (CD)62L levels, low CD101 levels and not IL‐5 dependent) 19 . At the steady state, intestinal rEos are not allergen‐induced and exhibit an immunosuppressive role, while iEos are antigen‐induced (with high Siglec‐8 and CD101 levels, low CD62L levels, and are IL‐5 dependent), which is proinflammatory 20 …”

“…18 Intestinal rEos can be distinguished from iEos by their surface receptor expression (intermediate Siglec-8 levels, a high cluster of differentiation (CD)62L levels, low CD101 levels and not IL-5 dependent). 19 At the steady state, intestinal rEos are not allergen-induced and exhibit an immunosuppressive role, while iEos are antigen-induced (with high Siglec-8 and CD101 levels, low CD62L levels, and are IL-5 dependent), which is proinflammatory. 20 Eosinophils in homeostasis, as postulated in the Local Immunity And/or Remodeling/Repair (LIAR) hypothesis, 21 are intrinsically homeostatic cells undertaking functional roles in local immunity through inflammation control, tissue remodeling, and epithelial barrier maintenance and repair.…”

Gut microbiota and intestinal immunity—A crosstalk in irritable bowel syndrome

“…Eloísa et al observed increased eosinophilic CRF secretion in the jejunal mucosa of IBS‐D patients, and it was significantly correlated with the severity of symptoms and depressive background [106]. While neuropeptides such as SP were shown to promote eosinophil recruitment and induce degranulation to release CRF, a process independent of the inflammatory pathway [116]. ANS mediates communication between CNS and gut [117].…”

Compilation of Evidence Supporting the Role of a T Helper 2 Reaction in the Pathogenesis of Acute Appendicitis

“…Eosinophil activation induces the release of active substances from their granules. Eosinophil-derived neurotoxin (EDN), eosinophil cationic protein (ECP), eosinophil peroxidase (EP) and major basic protein (MBP) are among the most studied eosinophil proteins, and are markers of eosinophil activation [79][80][81][82].…”