Sa1725 Human Intestinal Fibroblasts Are Novel Target Cells for Alpha-Melanocyte-Stimulating Hormone -Possible Implications for the Treatment of Stricturing Crohn's Disease With Melanocortin Peptides and Derivatives

Notably, DC T5 was absolutely critical for flagellin-induced IL-22 production, which is thought to play a key role in protecting the gut in infection, while both IEC and Hep T5 were important for robust systemic production of CXCL1 and IL-6.However, IEC T5 was the predominant determinant of intestinal and clinical phenotypes previously associated with loss of T5.Specifically, IEC-specific T5-deficient mice exhibited low-grade intestinal inflammation and metabolic syndrome, which were associated with altered microbiota composition, increased levels of fecal flagellin and LPS, decreased microbiota-epithelial distance, and reduced ability to quickly clear flagellated pathobionts.In contrast, mice lacking T5 in DC appeared similar to WT mice by these measures.While phenotype of mice lacking T5 in Hep remains under study, we note that loss of IEC T5 was not sufficient to recapitulate dietinduced liver disease previously associated with complete loss of T5 (steatosis), suggesting a role for Hep T5 in this disease model.CONCLUSION: IEC T5 is critical for keeping the microbiota in-check to minimize risk for developing diseases associated with intestinal inflammation.DC T5 may be important for protection against enteric pathogens while Hep T5 may protect against microbiota-mediated liver disease.