Сhanges of the functional phenotype of circulating monocytes during pregnancy

Rearrangement of the immune system during pregnancy is a strictly controlled, dynamic process in which the first and third trimesters are, respectively, pro-inflammatory, and anti-inflammatory periods. However, monocyte involvement in regulating the pro/anti-inflammatory balance remains poorly understood. The functional phenotype of monocytes is known to depend on their subsets assessed by CD14 and CD16 expression, and is associated with expression of M1(CCR2)- and M2(CD206) molecules, associated with pro- and anti-inflammatory activity, respectively. Here we have investigated the expression of CCR2 and CD206 in classical (CD14⁺⁺CD16^- , cMo), intermediate (CD14⁺⁺CD16⁺, iMo), and non-classical monocytes (CD14⁺CD16⁺⁺, nMo) in pregnant women at different gestational ages in comparison with nonpregnant women. The study included 14 pregnant women in the first trimester, 20 in the second trimester, 26 in the third trimester, and 29 fertile non-pregnant women. One-way analysis of variance in these groups revealed significant differences CCR2 and CD206 expression (more pronounced in classical and intermediate monocytes and stronger in relation to CD206 expression). Overall, monocytes from pregnant women had decreased CCR2- and increased CD206 expression, suggesting a shift towards an anti-inflammatory profile. These changes appeared in the first trimester (increased CD206 mean fluorescence intensity [MFI] in cMo and iMo, p < 0.05) and reached their maximum in the second trimester, manifested by significant increase in CD206 and decrease in CCR2 expression (% of cells, MFI) in all monocyte subsets. In the third trimester, CD206⁺ cMo decreased, as compared to the second trimester (p < 0.05), and the percentage of CCR2⁺ cMo and iMo increased. Of note, these changes in the first and third trimesters were combined with increased pro-inflammatory expression profile of non-classical monocytes which was restricted by the non-classical monocyte subpopulation in the first trimester, then being mediated by intermediate and non-classical monocytes in the third trimester. The data obtained suggest involvement of monocytes in regulation of the pro- and anti-inflammatory balance during pregnancy, with predominant development of the M2 profile in classical monocytes during the first and third trimesters, and in all monocyte subsets over second trimester, along with increase in the M1 proinflammatory profile of intermediate and non-classical monocytes in the first and third trimesters.

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