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Glucocorticoid-induced leucin zipper (GILZ) mediates the effects of glucocorticoids in immune cells, but little is known about its role in both the gastro-intestinal (GI) mucosa and inflammatory bowel diseases (IBD) in humans. To investigate the GILZ protein expression profile in the GI tract, mucosal biopsies from 80 patients were retrospectively enrolled in this study and subdivided into three groups: 1) patients without clinical-endoscopic and histological evidence of IBD; 2) IBD patients; 3) patients with chronic atrophic gastritis (CAG) and Barrett esophagus (BE), both characterized by intestinal metaplasia (IM). GILZ expression was assessed by immunohistochemical and immunofluorescence methods. Our results showed that GILZ protein was strongly expressed in the secretory cells in healthy mucosa. GILZ expression was reduced in goblet cells in active disease, whereas it was restored in quiescent diseases. Conversely, entero-endocrine cells were not involved in such inflammation-driven dynamics, as GILZ expression remained detectable in active disease. Moreover, GILZ was expressed in IM, but was limited to CAG, and was not detected in BE. In summary, GILZ acts as a secretory protein in the GI mucosa in healthy, hyperplastic and metaplastic conditions. Its secretion by goblet cells is mostly affected by neutrophils mucosal infiltration and seems to be directly related to active mucosal inflammation in IBD. Overall, our findings suggest that GILZ is a suitable molecule to be considered as a histological marker of mucosal healing.

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.