| 抄録 |
【purpose】dnTGF-βRII mouse manifests much of the clinical pathology found in patients with IBD. We hypothesized that the lack of normal TGF-β signaling within CD4+ and CD8+ T cells was a result of miRNA expression and thereby contributes to breakdown of tolerance and ultimate colonic destruction. 【methods】To address this problem, we took advantage of our ability to isolate well-defined populations of T cell subsets, including CD4 and CD8 T cells, but also naive (CD62L+CD44-) and effector (CD62L-CD44+) CD4 and CD8 T cell populations. Furthermore, we isolated lymphoid cells from liver, lung, spleen, thymus and mesenteric lymph node for both dnTGF-βRII and control B6 mice at 2 and 9 weeks of age by magnetic bead separation and cell sorting. Total RNA was extracted, cDNA synthesized and miRNA profiling determined by an EXIQON miRNA PCR array. Overall we analyzed 375 miRNA genes. 【results】miR-21 in dnTGF-βRII mice was significantly overexpressed in CD4+ and CD8+ T cells isolated from spleen, liver, mLN, and colon in dnTGF-βRII mice. Furthermore, it was the effector CD4+ and CD8+ T cell population that highly expressed miR-21 in dnTGF-βRII mice. We submit that miR-21 expression is critical to T cell autoreactivation. 【conclusion】Our data provide new insight not only into this model, but also reflects on the potential of miRNA analysis for dissecting other dysregulated and/or inflammatory processes. |
