Jiabin Ren1,2, Weihong Zeng3, Fuju Tian3, Siming Zhang4, Fan Wu3, Xiaoli Qin3, Yan Zhang5, Yi Lin3. 1. Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. 2. Shanghai Key Laboratory of Gynecologic Oncology, Shanghai, China. 3. International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. 4. Department of Obstetrics and Gynecology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China. 5. Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, China.
Abstract
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.
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.