Amniotic mesenchymal stem cells regulate T cell immunity in patients with rheumatoid arthritis through PGE2/EP2 pathway
Objective To investigate the effect of human amniotic mesenchymal stem cells(AMSCs)on the reg-ulation of T cell immunity in rheumatoid arthritis(RA)patients and the mechanism involved in the PGE2/EP2 pathway.Methods T lymphocytes from peripheral blood of RA patients and AMSCs were co-cultured without contact in culture media supplemented with RA autologous plasma.T lymphocyte sub-populations and inflamma-tory factors of the culture supernatant were detected by flow cytometry.PGE2 and IL-6 were detected by ELISA.PI3K,Akt,and their phosphorylated protein levels were detected by Western blot.Results AMSCs significantly decreased the proliferation of T lymphocytes of RA patients and the proportion of Th17 cells,while they increased the proportion of Treg cells and the ratio of Treg/Th17.Inflammatory factor IL-17 content was decreased in the co-culture supernatant.These effects could be blocked by the EP2 receptor antagonist AH6809 at 40 nmol/L.Compared with the AMSCs group,the levels of IL-1 β,IL-6,and IL-8 in the cultured medium were significantly reduced,but there was no significant difference between the EP2 receptor antagonist group and the culture group.AMSCs significantly heightened the level of p-PI3K,and decreased the level of p-AKT protein in T lym-phocytes.EP2 receptor antagonists could only reverse the down-regulation of p-AKT protein by AMSCs.Conclusion AMSCs inhibits T cells proliferation,up-regulates Treg/Th17,and down-regulates IL-17 secretion in RA patients.The mechanism is related to activation of PGE2/EP2 pathway.
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