H2 cytokine production. Others have observed elevated mucosal expression of the

Author manuscript; obtainable in PMC 2014 February 15.Rosen et al.Pagetogether, IL-33 augments T cell proinflammatory Th2 and Th1 cytokine secretion, even in STAT6-/- mice.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptDISCUSSIONIn the present study, we demonstrate a vital function for STAT6 inside the pathogenesis of oxazolone colitis, a murine model with T, but rather mediated by phosphoinositide three kinase (PI3K) signaling (41). We phenotypic and immunologic similarities to human UC. We assessed mRNA expression for both the soluble (sST2) and membrane-bound (ST2L) isoforms in the receptor in both colon tissue and MLN cells from these mice and found no variations in expression of either isoform amongst WT ETOH, WT OXA, and STAT6-/- OXA mice (Supplemental Figure 1). TakenJ Immunol. Author manuscript; obtainable in PMC 2014 February 15.Rosen et al.Pagetogether, IL-33 augments T cell proinflammatory Th2 and Th1 cytokine secretion, even in STAT6-/- mice.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptDISCUSSIONIn the present study, we demonstrate an essential part for STAT6 within the pathogenesis of oxazolone colitis, a murine model with phenotypic and immunologic similarities to human UC. In association with decreased colitis severity, STAT6-/- mice demonstrate lowered epithelial claudin-2 expression, decreased tissue mRNA expression of your Th2-inducing cytokines IL-33 and TSLP, and reduced MLN cell proinflammatory cytokine secretion.H2 cytokine production. Others have observed enhanced mucosal expression of your IL-33 receptor, ST2 in intestinal inflammation (29). We assessed mRNA expression for both the soluble (sST2) and membrane-bound (ST2L) isoforms from the receptor in both colon tissue and MLN cells from these mice and found no differences in expression of either isoform amongst WT ETOH, WT OXA, and STAT6-/- OXA mice (Supplemental Figure 1). TakenJ Immunol. Author manuscript; accessible in PMC 2014 February 15.Rosen et al.Pagetogether, IL-33 augments T cell proinflammatory Th2 and Th1 cytokine secretion, even in STAT6-/- mice.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptDISCUSSIONIn the present study, we demonstrate a vital role for STAT6 within the pathogenesis of oxazolone colitis, a murine model with phenotypic and immunologic similarities to human UC. In association with lowered colitis severity, STAT6-/- mice demonstrate lowered epithelial claudin-2 expression, lowered tissue mRNA expression of your Th2-inducing cytokines IL-33 and TSLP, and reduced MLN cell proinflammatory cytokine secretion. The existing literature reveals varying contributions of STAT6 to intestinal inflammation according to the model studied. In contrast to our findings with oxazolone colitis, other folks observed exacerbation of acute dextran sulfate sodium (DSS)-induced colitis in STAT6-/- mice (30). While Th2 inflammation has been implicated in chronic models of DSS colitis, acute DSS colitis has been linked predominantly with Th1 inflammation (31, 32). The truth is, DSS colitis will not require T cells because it happens in extreme combined immunodeficient BALB/c mice (33). Within the IL-4-dependent TCR-/- model of colitis, Okuda et al. discovered no effect of STAT6 genetic deletion on colitis development, supporting a function for STAT6independent IL-4 signaling in intestinal inflammation and Th2 cell differentiation (34). Their findings are in line with our observations that tissue IL-13 expression persisted and colitis was not entirely prevented in STAT6-/- OXA mice. In a mouse coinfection model with the helminth Heligmosomoides polygyrus and also the Gram-negative bacterium Citrobacter rodentium, STAT6-/- mice exhibited significantly less intestinal inflammation title= srep32673 in association with reduced infiltration of colonic lamina propria alternatively activated macrophages (35).