Figure 1.

Crosstalk between neurons, immune cells, and epithelial cells controls colonic homeostasis. A vital interplay between neurons, immune cells, and epithelial cells is crucial for colonic homeostasis. Aberrant function of one or more of these players may cause inflammation. For instance, activated macrophages release IL-1ß which among other cytokines acts as a chemoattractant to human peripheral blood mononuclear cells (PBMCs) (45). On the other hand, IL-1ß increases TNF-α receptor expression in epithelial cells which may promote TNF-α-mediated inflammatory responses and subsequently colitis. Moreover, IL-1ß acts on peptidergic sensory neurons through induction of pro-inflammatory substance P (SP) release. SP in turn induces migration of polymorphonuclear leukocytes in vivo (46). In addition, epithelial IL-8 and KC induce immune cell infiltration into the colonic wall. IL-10 is an essential immunoregulatory cytokine (47). Epithelial cells from murine small intestine and colon express the IL-10 receptor and its stimulation blocks IFN-γ-mediated pro-inflammatory effects (48). Moreover, not only epithelial cells but also enteric neurons express cytokines and chemokines such as IL-8, whose neuronal production is promoted by IL-1ß via MAPK signaling pathways (49).