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Toll\u2010like receptors (TLRs) recognize microbial ligands and play a key role in host\u2013microbe interactions in health and disease. TLR13 has a well\u2010established function in enhancing host defenses against pathogenic bacteria. However, its role in maintaining intestinal homeostasis and controlling colitis\u2010associated colon cancer (CAC) is largely unknown. This study aimed to investigate the involvement of TLR13\u2010mediated signaling in intestinal homeostasis and colonic tumorigenesis using <jats:italic>ex vivo<\/jats:italic> cell and <jats:italic>in vivo<\/jats:italic> CAC animal model. <jats:italic>Tlr13<\/jats:italic>\u2010deficient mice were prone to dextran sodium sulfate (DSS)\u2010induced colitis. During the early stages of the CAC regimen (AOM\/DSS\u2010treated), <jats:italic>Tlr13<\/jats:italic> deficiency led to severe ulcerative colitis. Moreover, <jats:italic>Tlr13<\/jats:italic>\u2010deficient mice exhibited increased intestinal permeability, as evidenced by elevated levels of fluorescein isothiocyanate (FITC)\u2010dextran, endotoxins, and bacterial translocation. Enhanced cell survival and proliferation of colonic intestinal cells were observed in <jats:italic>Tlr13<\/jats:italic>\u2010deficient mice. A transcriptome analysis revealed that <jats:italic>Tlr13<\/jats:italic> deficiency is associated with substantial changes in gene expression profile of colonic tumor tissue. <jats:italic>Tlr13\u2010<\/jats:italic>deficient mice were more susceptible to CAC, with increased production of interleukin (IL)\u20106, IL\u201012, and TNF\u2010\u03b1 cytokines and enhanced STAT3, NF\u2010\u03baB, and MAPK signaling in colon tissues. These findings suggest that TLR13 plays a protective role in maintaining intestinal homeostasis and controlling CAC. Our study provides a novel perspective on intestinal health via TLR13\u2010mediated signaling, which is crucial for deciphering the role of host\u2010microbiota interactions in health and disease.<\/jats:p>","DOI":"10.1002\/ijc.35089","type":"journal-article","created":{"date-parts":[[2024,7,11]],"date-time":"2024-07-11T08:37:41Z","timestamp":1720687061000},"page":"1858-1873","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Toll\u2010like receptor 13\u2010mediated signaling protects against the development of colon cancer"],"prefix":"10.1002","volume":"155","author":[{"given":"Asma","family":"Rafique","sequence":"first","affiliation":[{"name":"College of Medicine, and Jeju Research Center for Natural Medicine Jeju National University  Jeju South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irshad","family":"Ali","sequence":"additional","affiliation":[{"name":"College of Medicine, and Jeju 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