Chitinase 3-like 1 synergistically activates IL6-mediated STAT3 phosphorylation in intestinal epithelial cells in murine models of infectious colitis

Background: Chitinase 3-like 1 (CHI3L1) is an inducible molecule on intestinal epithelial cells during the development of inflammatory bowel disease. Methods: To investigate the role of CHI3L1 in bacterial infectious colitis, we orally inoculated pathogenic Salmonella typhimurium and potentially pathogenic adherent-invasive Escherichia coli (AIEC) LF82 virulent strain into C57Bl/6 wild-type mice or CHI3L1 knockout (KO) mice. Results: Both S. typhimurium and AIEC LF82 were found to efficiently induce severe intestinal inflammation in wild-type mice but not in CHI3L1 KO mice. These bacteria-infected CHI3L1 KO mice exhibit decreased cellular infiltration, bacterial translocation, and production of interleukin (IL)-6 and IL-22, as compared with those of wild-type mice. More importantly, CHI3L1 KO mice displayed aberrant STAT3 activation after bacterial infections. Co-stimulation of CHI3L1 and IL-6, but not IL-22, synergistically activates STAT3 signaling pathway in intestinal epithelial cells in an NF-κB/MAPK-dependent manner. Conclusions: CHI3L1 promotes the onset of selected gram-negative bacterial infectious colitis through IL-6/STAT3 pathway.