title: Myeloid-derived suppressor cells are essential for maintaining feto-maternal immunotolerance via STAT3 signaling in mice.
abstract: Maternal immune system tolerance to the semiallogeneic fetus is essential for a successful pregnancy; however, the mechanisms underlying this immunotolerance have not been fully elucidated. Here, we demonstrate that myeloid-derived suppressor cells play an important role in maintaining feto-maternal tolerance. A significant expansion of granulocytic myeloid-derived suppressor cells was observed in multiple immune organs and decidual tissues from pregnant mice. Pregnancy-derived granulocytic myeloid-derived suppressor cells suppressed T cell responses in a reactive oxygen species-dependent manner and required direct cell-cell contact. Mechanistic studies showed that progesterone facilitated differentiation and activation of granulocytic myeloid-derived suppressor cells, mediated through STAT3 signaling. The STAT3 inhibitor JSI-124 and a specific short hairpin RNA completely abrogated the effects of progesterone on granulocytic myeloid-derived suppressor cells. More importantly, granulocytic myeloid-derived suppressor cell depletion dramatically enhanced the abortion rate in normal pregnant mice, whereas adoptive transfer of granulocytic myeloid-derived suppressor cells clearly reduced the abortion rate in the CBA/J X DBA/2J mouse model of spontaneous abortion. These observations collectively demonstrate that granulocytic myeloid-derived suppressor cells play an essential role in the maintenance of fetal immunotolerance in mice. Furthermore, our study supports the notion that in addition to their well-recognized roles under pathologic conditions, myeloid-derived suppressor cells perform important functions under certain physiologic circumstances.
authors.affiliation: Program in Immunology, Affiliated Guangzhou Women and Children's Medical Center, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China; Institute of Human Virology, Sun Yat-sen University, Guangzhou, China;
authors.forename: Ting
authors.initials: T
authors.lastname: Pan
authors.affiliation: Program in Immunology, Affiliated Guangzhou Women and Children's Medical Center, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China; Institute of Human Virology, Sun Yat-sen University, Guangzhou, China;
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Institute of Human Virology, Sun Yat-sen University, Guangzhou, China;
authors.forename: Li Mei
authors.initials: LM
authors.lastname: Zhong
authors.affiliation: Institute of Human Virology, Sun Yat-sen University, Guangzhou, China;
authors.forename: Mao Hua
authors.initials: MH
authors.lastname: Shi
authors.affiliation: Institute of Human Virology, Sun Yat-sen University, Guangzhou, China;
authors.forename: Xiao Bing
authors.initials: XB
authors.lastname: Duan
authors.affiliation: Institute of Human Virology, Sun Yat-sen University, Guangzhou, China;
authors.forename: Kang
authors.initials: K
authors.lastname: Wu
authors.affiliation: Institute of Human Virology, Sun Yat-sen University, Guangzhou, China;
authors.forename: Qiong
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Institute of Human Virology, Sun Yat-sen University, Guangzhou, China;
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
authors.affiliation: Institute of Human Virology, Sun Yat-sen University, Guangzhou, China;
authors.forename: Jian Yang
authors.initials: JY
authors.lastname: Wei
authors.affiliation: Institute of Human Virology, Sun Yat-sen University, Guangzhou, China;
authors.forename: Xing Ru
authors.initials: XR
authors.lastname: Ma
authors.affiliation: Department of Gynecology, Guangzhou Women and Children's Medical Center, Guangzhou, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Shi
authors.affiliation: Institute of Human Virology, Sun Yat-sen University, Guangzhou, China; Key Laboratory of Tropical Disease Control, Chinese Ministry of Education, Sun Yat-sen University, Guangzhou, China; and.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Program in Immunology, Affiliated Guangzhou Women and Children's Medical Center, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China; Institute of Human Virology, Sun Yat-sen University, Guangzhou, China; Key Laboratory of Tropical Disease Control, Chinese Ministry of Education, Sun Yat-sen University, Guangzhou, China; and zhouj72@mail.sysu.edu.cn.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
mesh_terms: D000022:Abortion, Spontaneous; D019264:Adoptive Transfer; D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D005260:Female; D006098:Granulocytes / Q000276:immunology* / Q000378:metabolism; D007108:Immune Tolerance / Q000276:immunology*; D008297:Male; D033261:Maternal-Fetal Relations / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D000072737:Myeloid-Derived Suppressor Cells / Q000276:immunology* / Q000378:metabolism; D011247:Pregnancy; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human
keywords: MDSC; pregnancy; progesterone