Jinlu Ji1, Hui Zhai2, Hui Zhou1, Su Song2, Gil Mor1,3, Aihua Liao1. 1. Institute of Reproductive Health, Center for Reproductive Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 2. Wuhan Tongji Reproductive Medicine Hospital, Wuhan, China. 3. C.S. Mott Center for Human Growth and Development, Wayne State University School of Medicine, Detroit, Michigan.
Abstract
PROBLEM: Vitamin D has a pivotal role in regulating immune responses in women with recurrent pregnancy loss (RPL), but the underlying mechanism has not been completely clarified. This study aimed to determine the correlation between vitamin D and Treg/Th17 and the effects of vitamin D supplementation on Treg/Th17 balance in RPL patients. METHODS OF STUDY: The level of vitamin D was determined in women with normal pregnancy and RPL by electrochemiluminescence. The percentages of CD4+ Foxp3+ Treg, CD4+ IL-17+ Th17, and CD4+ Foxp3+ IL-17+ T cells were determined by flow cytometry before and after vitamin D supplementation. Changes about Treg/Th17 balance after culturing with active vitamin D in vitro were determined. Vitamin D metabolic activity of peripheral blood mononuclear cells was also detected by RT-PCR. RESULTS: Compared with normal pregnancy, both the level of vitamin D and the Treg/Th17 ratio were significantly decreased in women with RPL. There was a positive correlation between the level of vitamin D and the Treg/Th17 ratio in the RPL group. Within the RPL group, those who received 2 months of vitamin D supplementation showed a significantly increased Treg/Th17 ratio compared with those without vitamin D supplementation. In vitro analysis showed that adding different concentrations of active vitamin D increased the Treg/Th17 ratio, also the mRNA levels of the vitamin D receptor and the metabolic enzyme CYP24A1 increased significantly. CONCLUSION: The occurrence of RPL may be related to vitamin D insufficiency and Treg/Th17 imbalance. The Treg/Th17 imbalance seen in women with RPL can be restored by vitamin D supplementation both in vivo and in vitro. The effects of vitamin D on the immune regulation of RPL indicate that vitamin D might be used as an alternative therapy in the future.
PROBLEM: Vitamin D has a pivotal role in regulating immune responses in women with recurrent pregnancy loss (RPL), but the underlying mechanism has not been completely clarified. This study aimed to determine the correlation between vitamin D and Treg/Th17 and the effects of vitamin D supplementation on Treg/Th17 balance in RPLpatients. METHODS OF STUDY: The level of vitamin D was determined in women with normal pregnancy and RPL by electrochemiluminescence. The percentages of CD4+ Foxp3+ Treg, CD4+ IL-17+ Th17, and CD4+ Foxp3+ IL-17+ T cells were determined by flow cytometry before and after vitamin D supplementation. Changes about Treg/Th17 balance after culturing with active vitamin D in vitro were determined. Vitamin D metabolic activity of peripheral blood mononuclear cells was also detected by RT-PCR. RESULTS: Compared with normal pregnancy, both the level of vitamin D and the Treg/Th17 ratio were significantly decreased in women with RPL. There was a positive correlation between the level of vitamin D and the Treg/Th17 ratio in the RPL group. Within the RPL group, those who received 2 months of vitamin D supplementation showed a significantly increased Treg/Th17 ratio compared with those without vitamin D supplementation. In vitro analysis showed that adding different concentrations of active vitamin D increased the Treg/Th17 ratio, also the mRNA levels of the vitamin D receptor and the metabolic enzyme CYP24A1 increased significantly. CONCLUSION: The occurrence of RPL may be related to vitamin Dinsufficiency and Treg/Th17 imbalance. The Treg/Th17 imbalance seen in women with RPL can be restored by vitamin D supplementation both in vivo and in vitro. The effects of vitamin D on the immune regulation of RPL indicate that vitamin D might be used as an alternative therapy in the future.