Introduction: T regulatory cells (Tregs) are known as immunoregulatory cells that are reduced in atherosclerosis. Tregs are a part of crosstalk between the immune system and lipoprotein metabolism, both of which are involved in atherosclerotic processes. Depletion of Tregs leads to impaired clearance of low density lipoprotein (LDL), and intracellular cholesterol homeostasis affects Treg cell development. Furthermore, the atherosclerotic environment affects the Treg cells' phenotype and plasticity. Plasticity between Tregs and Th17 cells has been a matter of investigation lately. We investigated the frequency of interleukin-17 (IL-17)-producing Tregs in the peripheral blood of patients with atherosclerosis.
Material and methods: We studied 10 non-diabetic patients with significant coronary artery disease (CAD) as the patient group, and seven non-diabetic individuals with normal coronary angiography/insignificant CAD as the control group. Peripheral blood mononuclear cells were stained with fluorescent antibodies to detect CD4, CD45RO, IL-17, and Foxp3 expression both before and after stimulation with PMA/Ionomycin. Cell enumeration was performed using flowcytometry and analysed using Mann-Whitney test.
Results: CD4+IL-17+Foxp3+ and CD4+IL-17+Foxp3- subsets showed higher frequencies in patients than in controls both before (p = 0.0031, p = 0.033, respectively) and after stimulation (p = 0.0027 and p = 0.0013, respectively). Interestingly, CD4+IL-17+Foxp3+ cells were almost exclusively CD45RO+ with a much higher frequency in patients than in controls (p = 0.0027, p = 0.0007). After stimulation, the frequency of CD4+CD45RO+IL-17+Foxp3+ lymphocytes increased to a greater extent in patients (p < 0.0001) than in controls.
Conclusions: Interleukin-17 production by an intermediate population with an activated Treg phenotype in our patients may point to the population heterogeneity or plasticity in Tregs during atherosclerotic inflammation.
Keywords: Foxp3; Treg; atherosclerosis; interleukin-17.