Association of GILZ with MUC2, TLR2, and TLR4 in Inflammatory Bowel Disease

Ulcerative colitis (UC) and Crohn's Disease (CD) are chronic relapsing inflammatory diseases that are caused by genetic, environmental, and immune factors. Treatment strategies are currently based on symptomatic control by immunosuppression. The glucocorticoid-induced leucine zipper (GILZ), a mediator of several effects of glucocorticoids, was recently found to be secreted by goblet cells and play a role in inflammatory bowel disease (IBD). This study investigates which genes GILZ is associated with in its role in intestinal barrier functions. We examined datasets from the Gene Expression Omnibus (GEO) and ArrayExpress profiles of the gut of healthy subjects (HSs), as well as UC and CD patients. The human colonic epithelial HT29 cell line was used for in vitro validation experiments. GILZ was significantly correlated with MUC2, TLR2, and TLR4. In particular, an inverse correlation was found between the GILZ and MUC2 in HS and patients with IBD, mostly in those with an active disease. Further, direct pairwise correlations for GILZ/TLR2 and GILZ/TLR4 were found in HSs and UC patients, but not in CD patients. Overall, our results reveal the crosstalk at the transcription level between the GILZ, MUC2, and TLRs in the mucosal barrier through common pathways, and they open up new perspectives in terms of mucosal healing in IBD patients.

Automated summary

Ulcerative colitis (UC) and Crohn's Disease (CD) are chronic relapsing inflammatory diseases caused by genetic, environmental, and immune factors. The glucocorticoid-induced leucine zipper (GILZ) plays a role in inflammatory bowel disease (IBD) and is associated with genes MUC2, TLR2, and TLR4 in the mucosal barrier. Direct correlations between GILZ/TLR2 and GILZ/TLR4 were found in healthy subjects (HSs) and UC patients, while an inverse correlation was observed between GILZ and MUC2 in HS and IBD patients, particularly those with active disease.