Fig. 4
The opposing roles of Th17-producing cytokines in IBD pathogenesis. Th17-producing cytokines, including IL-22, IL-17, and GM-CSF, influence diverse biological processes and can act both protectively and pathogenically in inflammatory bowel disease (IBD). The effects of these cytokines can be categorized into direct effects on IECs and indirect effects via myeloid subsets. In the context of their direct effects on IECs, these cytokines regulate the gut microbiota through the production of antimicrobial peptides and increase the fucosylation of membrane proteins on IECs. These cytokines also promote gut stem cell turnover, inhibit apoptosis induced by injury, and strengthen tight junctions between IECs, thereby maintaining gut integrity. Collectively, these effects play a protective role in IBD. In the indirect effect mediated through myeloid cell subsets, IL-22 and IL-17 enhance chemokine production by IECs, which in turn recruit neutrophils and monocytes. GM-CSF is involved in neutrophil activation, monocyte maturation, and eosinophil differentiation. The recruited and activated myeloid cells contribute to bacterial killing through phagocytosis. However, these cells can also mediate inflammation via cytokine production (i.e., IL-23 and IL-1Ī²) and tissue destruction, thereby exacerbating the pathology of IBD
