Immunopathological Mechanisms Operative in Patients with Collagenous Colitis, Ulcerative Colitis and Non-Inflamed, Normal Colon.
Vera Genitsch, Daniela Kassahn, Anton Johner, Christoph Mueller. University of Berne, Switzerland
Background: While the understanding of the cellular and molecular mechanisms involved in the pathogenesis of inflammatory bowel diseases (IBD) increased substantially over the past few years, relatively little is known on the mechanisms involved in the aetiology of collagenous colitis. The pathogenetic relationship of collagenous colitis (CC) and inflammatory bowel diseases, particularly, with ulcerative colitis (UC) continues to be debated. In this study we aimed to improve our understanding about the aethiopathogenesis of CC by a detailed phenotypical and functional characterization of the involved cell types. Special emphasis was on the respective contribution of the local innate and adaptive immune system.
Design: We compared the expression of genes related to macrophages, T-lymphocytes and intestinal epithelial cells from CC, UC and healthy control (HC) patients (N=10, each), using RNA isolated from tissue sections of formalin-fixed, paraffin-embedded colonic biopsies for subsequent quantitative realtime PCR.
Results: In UC the expression of the T-cell lineage – specific transcription factors t-bet and GATA3 is increased compared to HC and CC, indicating a higher frequency of effector CD4+ T-cells in UC. Furthermore, the expression of TGFb1 and TGFb3 is exclusively increased in UC and is associated with elevated FoxP3 expression, suggesting a counter-regulation to chronic inflammation through an increased local accumulation of Treg's in UC, but not in CC. Triggering receptor expressed on myeloid cells 1 (TREM1) mRNA is markedly increased in UC, but almost completely absent in CC and HC, whereas TREM2 mRNA expression is comparably low in UC and CC. This may indicate differential macrophage differentiation (M1vs.M2). Transcription of the cytokine TSLP, which is preferentially expressed in intestinal epithelium, is reduced in CC in comparison to HC.
Conclusions: The established methodology is suitable to determine distinct gene expression profiles using paraffin embedded tissues. Preliminary data indicate differences in the gene expression patterns in the myeloid, epithelial and T-cell compartment in the colonic mucosa of UC, CC, and HC. The cell-type specific isolation of mRNA form colonic tissue sections by laser capture microdissection, also in combination with adapted immunostaining protocols, will further allow to define distinct, cell type-specific pathogenetic pathways operative in CC, UC and HC.
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 17, Wednesday Morning