ENTPD1, NT5E, ADORA2A, FOXP3 and RORγ gene expression in peripheral blood of patients with ulcerative colitis

Development of ulcerative colitis (UC) is accompanied by activation of the purinergic signaling pathway and an increased level of extracellular adenosine. Adenosine is involved in regulating the balance of pro-inflammatory T-helper type 17 (Th17) cells and immunosuppressive regulatory T-cells (Treg), Their disturbance is believed to be one of the main immune factors causing this disease. However, expression of genes encoding Treg cell and Th17 transcription factors (FOXP3 and RORγ, respectively) and genes encoding members of the CD39/CD73/A2AR signaling pathway (ENTPD1, NT5E, ADORA2A) in peripheral blood has not been studied enough. The purpose of our study was to evaluate the expression levels of ENTPD1, NT5E, ADORA2A, FOXP3 and RORγ genes in ulcerative colitis (UC). Thirty-eight patients were examined including 20 patients diagnosed with UC (15 patients on a basic therapy with 5-ASA derivatives, UC1 group); 5 patients treated with Prednisone (group UC2), and 18 apparently healthy people. Total RNA was isolated from peripheral blood leukocytes (PBLCs). The levels of gene transcripts were studied by real-time PCR technique. The ENTPD1 gene mRNA content in UC patients on a basic therapy with 5-ASA derivatives was higher than in healthy people (p = 0.0045). The levels of NT5E and ADORA2A transcripts in the PBLCs of patients in the UC1 group were higher than those of patients in the UC2 group (p = 0.0486 and p = 0.0289, respectively) and healthy individuals (p = 0.0007 and p < 0.001, respectively). The mRNA content of FOXP3 gene in PBLCs of the UC1 group of patients was higher than in conditionally healthy individuals (p = 0.0093). The level of RORγ gene expression in PBLCs of the patients from UC1 and UC2 groups was higher than in healthy individuals (p = 0.0005). Increased levels of FOXP3 and RORγ gene expression (the transcription factors of Treg and Th17 cells, respectively), were observed in PBLCs of UC patients on baseline therapy, whereas expression levels of these genes in prednisolone-treated UC patients did not differ from controls. Correlations between the expression levels of some genes under study were revealed in control persons and in the UC1 group.

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