| First Author | Rosen MJ | Year | 2013 |
| Journal | J Immunol | Volume | 190 |
| Issue | 4 | Pages | 1849-58 |
| PubMed ID | 23303670 | Mgi Jnum | J:193252 |
| Mgi Id | MGI:5468042 | Doi | 10.4049/jimmunol.1201373 |
| Citation | Rosen MJ, et al. (2013) STAT6 Deficiency Ameliorates Severity of Oxazolone Colitis by Decreasing Expression of Claudin-2 and Th2-Inducing Cytokines. J Immunol 190(4):1849-58 |
| abstractText | Patients suffering from ulcerative colitis (UC) exhibit chronic colonic inflammation caused by a dysregulated mucosal immune response and epithelial barrier disruption. Th2 cytokines, including IL-13, have been implicated in the pathogenesis of UC. IL-13 induces phosphorylation of STAT6, and we previously demonstrated increased epithelial p-STAT6 in children with UC. In this study, we investigated the role of STAT6 in oxazolone colitis, a murine model of UC, by inducing colitis in STAT6-deficient (STAT6(-/-)) and wild type (WT) mice. We observed increased epithelial cell, T cell, macrophage, and NKT cell STAT6 phosphorylation, as well as increased p-STAT6(+) IL-13-producing NKT cells, in colitic WT mice. Colitis was attenuated in STAT6(-/-) mice, with improvements in weight, colon length, and histopathology. There was decreased induction of the pore-forming tight junction protein claudin-2 in STAT6(-/-) mice. Similarly, short hairpin RNA STAT6 knockdown reduced claudin-2 induction and transepithelial resistance decrease in IL-13-treated human T84 cells. Tissue expression of IL-13, IFN-gamma, IL-17, and IL-10 mRNA was similarly induced in WT and STAT6(-/-) colitic mice; however, we observed increased mRNA expression for the Th2-inducing cytokines IL-33 and thymic stromal lymphopoietin in WT mice with colitis, which was abrogated in STAT6(-/-) mice. Mesenteric lymph node cells from STAT6(-/-) mice with colitis exhibited reduced secretion of IL-4, IL-5, IL-13, and IFN-gamma. IL-33 augmented mesenteric lymph node cell secretion of IL-5, IL-13, IL-6, and IFN-gamma. These data implicate STAT6 in the pathogenesis of colitis in vivo with important roles in altering epithelial barrier function and regulating Th2-inducing cytokine production. |
