The multiple faces of inflammatory enteric glial cells: is Crohn’s disease a gliopathy?

Abstract : Gone are the days when enteric glial cells (EGC) were considered merely as satellites of enteric neurons. Like their brain counterpart astrocytes, EGC express an impressive number of receptors for neurotransmitters and intercellular messengers, thereby contributing to neuroprotection and to the regulation of neuronal activity. EGC also produce different soluble factors that regulate neighboring cells among which are intestinal epithelial cells. A better understanding of EGC response to an inflammatory environment, often referred to as enteric glial reactivity, could help define the physiological role of EGC and the importance of this reactivity in maintaining gut functions. In chronic inflammatory disorders of the gut such as Crohn's disease (CD) and ulcerative colitis (UC), EGC exhibit abnormal phenotype and their neighboring cells are dysfunctional, but it remains unclear whether EGC are only passive bystanders or active players in the pathophysiology of both disorders. The aim of the current paper is to review the physiological roles and properties of EGC, their response to inflammation, their role in the regulation of the intestinal epithelial barrier and to discuss the emerging concept of CD as being an enteric gliopathy.