Abstract

Regulation of CD4+FOXP3+ T cells by CCL20/CCR6 axis in early unexplained recurrent miscarriage patients

Expression and function of CCR6/CCL20 in CD4+FOXP3+ regulatory T cells (Tregs) was investigated in unexplained recurrent miscarriage (URM) patients. Flow cytometry, reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay, western blots, and Transwell migration assays were used to analyze the expression and function of regulatory T cells in peripheral blood (PB) and decidual samples of women with URM and of healthy controls. Proportions of CD4+FOXP3+ T cells and CCR6+CD4+FOXP3+ T cells were lower in URM patients than in healthy controls for both PB lymphocytes and decidual samples (P FOXP3 and CCR6 mRNA were lower in URM patients than in control subjects for PB and decidual samples (P in vitro. Furthermore, CCL20-stimulated Tregs exhibited a 3.21-fold increase in migration and this was blocked using a neutralizing anti-CCL20 antibody. IL-10 concentration in culture supernatants of CD4+CD25+CD127dim/- Tregs of URM patients was significantly lower than that in controls. Anti-CCL20 antibody inhibited IL-10 and IL-4 expression but increased IFN-r and IL-17 levels when there was cell-cell contact between PB CD4+CD25+ T cells and CD4+CD25- T cells. No difference was detected when cell-cell contact was prevented by a semi-permeable Transwell membrane. CCL20-CCR6 could drive immune activity of CD4+FOXP3+ Tregs, followed by their migration to the feto-maternal microenvironment. These results elucidated the mechanism by which Tregs exert this suppressive effect.

• PDF