| First Author | Yang WH | Year | 2023 |
| Journal | iScience | Volume | 26 |
| Issue | 10 | Pages | 107883 |
| PubMed ID | 37752945 | Mgi Jnum | J:341196 |
| Mgi Id | MGI:7532229 | Doi | 10.1016/j.isci.2023.107883 |
| Citation | Yang WH, et al. (2023) Innate mechanism of mucosal barrier erosion in the pathogenesis of acquired colitis. iScience 26(10):107883 |
| abstractText | The colonic mucosal barrier protects against infection, inflammation, and tissue ulceration. Composed primarily of Mucin-2, proteolytic erosion of this barrier is an invariant feature of colitis; however, the molecular mechanisms are not well understood. We have applied a recurrent food poisoning model of acquired inflammatory bowel disease using Salmonella enterica Typhimurium to investigate mucosal barrier erosion. Our findings reveal an innate Toll-like receptor 4-dependent mechanism activated by previous infection that induces Neu3 neuraminidase among colonic epithelial cells concurrent with increased Cathepsin-G protease secretion by Paneth cells. These anatomically separated host responses merge with the desialylation of nascent colonic Mucin-2 by Neu3 rendering the mucosal barrier susceptible to increased proteolytic breakdown by Cathepsin-G. Depletion of Cathepsin-G or Neu3 function using pharmacological inhibitors or genetic-null alleles protected against Mucin-2 proteolysis and barrier erosion and reduced the frequency and severity of colitis, revealing approaches to preserve and potentially restore the mucosal barrier. |
