Eomesodermin regulate decidual CD4⁺T cell function during human early pregnancy

Decidual CD4⁺T (dCD4⁺T) cells play pivotal roles in inducing and maintaining maternal-fetal tolerance. Dysfunctional dCD4⁺T cells are associated with miscarriage. In the present study, we demonstrated that the T-box transcription factor protein eomesodermin (Eomes) was involved in the functional regulation of dCD4⁺T cells during early pregnancy. We concluded the higher Eomes expression dCD4⁺T cells during normal pregnancy, and the Eomes⁺dCD4⁺T cells displayed an active status and produced more Th2- and Treg type cytokines. Decreased number and altered function of Eomes⁺dCD4⁺T cells were observed in miscarriage. Progesterone, the traditional treatment for miscarriage, had no effect on Eomes expression by dCD4⁺T cells from normal pregnancy, but increased Eomes expression by dCD4⁺T cells from miscarriage. We also found the higher frequency of Eomes⁺dCD4⁺T cells from miscarriage in response to cyclosporine, tacrolimus, Trophoblasts, and HTR8/SVneo cell line, might provide new strategy for therapy to promote maternal-fetal tolerance and prevent pregnancy loss. These results indicated that Eomes might be promising early warming targets of miscarriage, though further studies are required to determine that the altered number and function of Eomes⁺dCD4⁺T cells are the cause or consequence of miscarriage.