title: IL-9 regulates intestinal barrier function in experimental T cell-mediated colitis.
abstract: As previous studies suggested that IL-9 may control intestinal barrier function, we tested the role of IL-9 in experimental T cell-mediated colitis induced by the hapten reagent 2,4,6-trinitrobenzenesulfonic acid (TNBS). The deficiency of IL-9 suppressed TNBS-induced colitis and led to lower numbers of PU.1 expressing T cells in the lamia propria, suggesting a regulatory role for Th9 cells in the experimental TNBS colitis model. Since IL-9 is known to functionally alter intestinal barrier function in colonic inflammation, we assessed the expression of tight junction molecules in intestinal epithelial cells of TNBS-inflamed mice. Therefore we made real-time PCR analyses for tight junction molecules in the inflamed colon from wild-type and IL-9 KO mice, immunofluorescent stainings and investigated the expression of junctional proteins directly in intestinal epithelial cells of TNBS-inflamed mice by Western blot studies. The results demonstrated that sealing proteins like occludin were up regulated in the colon of inflamed IL-9 KO mice. In contrast, the tight junction protein Claudin1 showed lower expression levels when IL-9 is absent. Surprisingly, the pore-forming molecule Claudin2 revealed equal expression in TNBS-treated wild-type and IL-9-deficient animals. These results illustrate the pleiotropic functions of IL-9 in changing intestinal permeability in experimental colitis. Thus, modulation of IL-9 function emerges as a new approach for regulating barrier function in intestinal inflammation.
authors.affiliation: Department of Medicine 1; University of Erlangen-Nuremberg; Kussmaul Research Campus ; Erlangen, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Gerlach
authors.affiliation: MRC Laboratory of Molecular Biology ; Cambridge, United Kingdom.
authors.forename: Andrew N
authors.initials: AN
authors.lastname: McKenzie
authors.affiliation: Department of Medicine 1; University of Erlangen-Nuremberg; Kussmaul Research Campus ; Erlangen, Germany.
authors.forename: Markus F
authors.initials: MF
authors.lastname: Neurath
authors.affiliation: Department of Medicine 1; University of Erlangen-Nuremberg; Kussmaul Research Campus ; Erlangen, Germany.
authors.forename: Benno
authors.initials: B
authors.lastname: Weigmann
keywords: CD, Crohn´s disease; IBD, Inflammatory bowel disease; IL-9, Interleukin-9; KO, knockout; Th9, T-helper cell type 9; TNBS, 2,4,6-trinitrobenzenesulfonic acid; RT-PCR, reverse transcription-polymerase chain reaction; UC, ulcerative colitis; WT, wild-type; IL-9; TNBS colitis; Th9 cells; claudins; intestinal epithelial cells; tight junctions
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