Myeloid-derived suppressor cells depletion may cause pregnancy loss via upregulating the cytotoxicity of decidual natural killer cells.

PROBLEM: Maternal immune system tolerance to the semiallogeneic fetus is critical for a successful pregnancy. Studies have shown that myeloid-derived suppressor cells (MDSCs) play an important role in maintaining feto-maternal tolerance. However, the mechanisms remain poorly understood.

METHODS

Flow cytometry was used to evaluate the percentage of MDSCs in an allogeneic-normal-pregnant mouse model during different periods of gestation. We further assessed the percentage of MDSCs and their subtypes (granulocytic MDSCs [GR-MDSCs] and monocytic MDSCs [MO-MDSCs]) in a spontaneous abortion mouse model. The levels of the immunosuppressive molecules ARG-1, iNOS, IL-10, and TGF-β in MDSCs were also evaluated. MDSCs were depleted by anti-Gr-1 injection, and the resorption rate was calculated. The cytotoxicity of decidual natural killer (NK) cells was evaluated, and the percentage of regulatory NK (NKreg) cells and regulatory T lymphocytes (Tregs) were evaluated.

RESULTS

Myeloid-derived suppressor cells was accumulated in a time-dependent manner during pregnancy. However, the percentage of MDSCs was decreased in the spontaneous abortion mice compared with that in the control mice. In addition, the levels of ARG-1, iNOS, IL-10, and TGF-β in MDSCs decreased differentially. Finally, depletion of MDSCs was associated with increased rates of resorption and the proportion of NKreg and Treg cells in uterine tissues; meanwhile, the cytotoxicity of decidual NK cells was upregulated by increasing the level of perforin, granzyme B, and natural killer group protein 2 D-activating NK receptor (NKG2D).

CONCLUSION

Depletion of MDSCs may cause pregnancy loss, while upregulating the cytotoxicity of decidual NK cells and increasing NKreg and Treg cell numbers.