Fanfan Li1, Jing Dang1, Min Jiang1,2, Mengzhou He1, Meitao Yang1, Jing Li1,3, Haiyan Hao1, Yuan Zhou1,4, Wei Zuo1,5, Yin Xie1, Dongrui Deng1. 1. Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. 2. Department of Gynecology and Obstetrics, Northern Jiangsu Province Hospital, Clinical Medical College, Yangzhou University, Jiangsu, China. 3. Faculty of Reproductive Medical Center of the Third Hospital, Zhengzhou University, Zhengzhou, Henan, China. 4. Department of Reproductive Medical Center, Tangdu Hospital, The Fourth Military Medical University, xi'an, China. 5. Faculty of Department of Orthopedics, Pu Ai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Abstract
PROBLEM: To understand the mechanisms of action of Tim-3 at the maternal-fetal interface and explore how Tim-3 might be involved in the pathogenesis of abortion by constructing an in vitro trophoblast-lymphocyte system. METHODS OF STUDY: Female CBA/J × male DBA/2 matings were used as the abortion-prone model and CBA/J × male BALB/c matings as control. The expression of Tim-3 at the maternal-fetal interface and in the peripheral blood lymphocytes was measured by immunohistochemistry and Western blotting. The proliferation index of lymphocytes and levels of Th1/Th2-derived cytokines in peripheral blood and in the co-culture system were determined using CCK-8 assay and ELISA, respectively. RESULTS: The expression level of Tim-3 was higher in abortion-prone matings than that of control (P < .05). A preponderance of Th1 was observed in the co-culture system in the abortion-prone mating group. Recombinant Tim-3 Ig reversed the imbalance of Th1/Th2 immunity of abortion-prone matings by suppressing the secretion of IFN-γ and IL-2 but had no direct effect on the generation of IL-4. CONCLUSION: Tim-3 might contribute to successful pregnancy by restraining Th1 bias, and the maternal immune system might develop a strategy including upregulation of Tim-3 at the maternal-fetal interface and in peripheral blood so as to maintain moderate inflammatory responses against miscarriage.
PROBLEM: To understand the mechanisms of action of Tim-3 at the maternal-fetal interface and explore how Tim-3 might be involved in the pathogenesis of abortion by constructing an in vitro trophoblast-lymphocyte system. METHODS OF STUDY: Female CBA/J × male DBA/2 matings were used as the abortion-prone model and CBA/J × male BALB/c matings as control. The expression of Tim-3 at the maternal-fetal interface and in the peripheral blood lymphocytes was measured by immunohistochemistry and Western blotting. The proliferation index of lymphocytes and levels of Th1/Th2-derived cytokines in peripheral blood and in the co-culture system were determined using CCK-8 assay and ELISA, respectively. RESULTS: The expression level of Tim-3 was higher in abortion-prone matings than that of control (P < .05). A preponderance of Th1 was observed in the co-culture system in the abortion-prone mating group. Recombinant Tim-3 Ig reversed the imbalance of Th1/Th2 immunity of abortion-prone matings by suppressing the secretion of IFN-γ and IL-2 but had no direct effect on the generation of IL-4. CONCLUSION:Tim-3 might contribute to successful pregnancy by restraining Th1 bias, and the maternal immune system might develop a strategy including upregulation of Tim-3 at the maternal-fetal interface and in peripheral blood so as to maintain moderate inflammatory responses against miscarriage.