Interplay between dysregulated immune system and the footprints of blood-borne miRNAs in treatment naive Crohn disease and ulcerative colitis patients

Dysregulated T cell mediated immune response is the hallmark of inflammatory bowel diseases (IBD), Crohn's disease and ulcerative colitis. miRNAs are established regulators of biological processes, with clear contribution to the pathophysiology of several diseases. Here, we attempt to elucidate the correlation between dysregulated immune system and altered miRNA signatures in IBD patients. Furthermore, we also aim to identify differentially expressed miRNAs that could potentially serve as differential diagnostic markers of CD and UC. High-throughput small RNA sequencing was conducted to quantify circulating miRNAs in 27 participants - 8 CD, 10 UC and 9 healthy volunteers. To describe immune-dysregulation, circulating T-cell related cytokines were determined via bead array. Additionally, in IBD patients, the distribution of T cell subpopulations was also determined in circulation and in tissue biopsy samples using multicolor flow cytometry. Based on small RNA sequencing results, 14 miRNAs showed significant expression differences between IBD and control group after qRT-PCR validation. Five miRNAs were found to exhibit significantly different expression and high discriminatory potential between CD and UC patients. Furthermore, circulating IL-22 and IFN-gamma levels were significantly higher in IBD. Notably, miRNAs exhibited several strong negative and positive correlations with cytokine levels and with T-cell subset distribution in circulation and tissue samples, with disease specific association pattern. We identified differentially expressed miRNAs in IBD patients groups. A subset of these miRNAs shows promising diagnostic value for distinguishing CD from UC. Thereby scrutinizing miRNA expression in blood samples of IBD patients might holds diagnostic and monitoring potential. Our results confirmed that, dysregulated miRNAs reflect the underlying immune dysregulation and may contribute to IBD diseases pathology.