IDENTIFICATION AND VALIDATION OF NOVEL CROHN'S DISEASE-ASSOCIATED LONG INTERGENIC NON-CODING RNAS FROM INTESTINAL CD4(+) T CELLS
Gastroenterology(2019)
Abstract
mice compared with littermate control animals.An adoptive transfer model of colitis showed that BMI1 -/-Tregs failed to suppress colitis in vivo.Mice injected with BMI1 -/-Tregs had significant differences in weights (1.1 ± 0.11 fold change from initial weight vs 1.4 ± 0.05, p=0.005) and increased disease activity index (2.6 ± 0.63 vs 0.42 ± 0.32, p=0.0048) when compared to mice injected with WT Tregs.Histopathology confirmed moderate colitis and enteritis in the mice injected with BMI1-deficient Tregs.Cytokine analysis from peripheral blood showed an increased secretion of TNF (76.6 ± 18.8 pg/dL vs 6.0 ± 3.2, p=0.005) and IFNg (10.0 ± 2.3 pg/dL vs 1.2 ± 0.7, p=0.006) in the mice receiving the BMI-deficient Tregs vs WT Tregs.Together these data support a PRC2-independent role of PRC1-mediated regulation of enhancer gene networks key to the development of human IBD.
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Key words
Crohn's Disease
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