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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\u2013cell 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.<\/jats:p>","DOI":"10.1189\/jlb.1a1015-481rr","type":"journal-article","created":{"date-parts":[[2016,9,1]],"date-time":"2016-09-01T07:13:29Z","timestamp":1472714009000},"page":"499-511","source":"Crossref","is-referenced-by-count":80,"title":["Myeloid-derived suppressor cells are essential for maintaining feto-maternal immunotolerance via STAT3 signaling in mice"],"prefix":"10.1093","volume":"100","author":[{"given":"Ting","family":"Pan","sequence":"first","affiliation":[{"name":"Program in Immunology, Affiliated Guangzhou Women and Children\u2019s Medical Center, Zhongshan School of Medicine, Sun Yat-sen University , Guangzhou , China"},{"name":"Institute of Human Virology, Sun Yat-sen University , Guangzhou , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufeng","family":"Liu","sequence":"additional","affiliation":[{"name":"Program in Immunology, Affiliated Guangzhou Women and Children\u2019s Medical Center, Zhongshan School of Medicine, Sun Yat-sen University , Guangzhou , China"},{"name":"Institute of Human Virology, Sun Yat-sen University , Guangzhou , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li Mei","family":"Zhong","sequence":"additional","affiliation":[{"name":"Institute of Human Virology, Sun Yat-sen University , Guangzhou , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mao Hua","family":"Shi","sequence":"additional","affiliation":[{"name":"Institute of Human Virology, Sun Yat-sen University , Guangzhou , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao Bing","family":"Duan","sequence":"additional","affiliation":[{"name":"Institute of Human Virology, Sun Yat-sen University , Guangzhou , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang","family":"Wu","sequence":"additional","affiliation":[{"name":"Institute of Human Virology, Sun Yat-sen University , Guangzhou , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiong","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Human Virology, Sun Yat-sen University , Guangzhou , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Human Virology, Sun Yat-sen University , Guangzhou , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian Yang","family":"Wei","sequence":"additional","affiliation":[{"name":"Institute of Human Virology, Sun Yat-sen University , Guangzhou , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing Ru","family":"Ma","sequence":"additional","affiliation":[{"name":"Institute of Human Virology, Sun Yat-sen University , Guangzhou , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Guangzhou Women and Children\u2019s Medical Center , Guangzhou , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Human Virology, Sun Yat-sen University , Guangzhou , China"},{"name":"Key Laboratory of Tropical Disease Control, Chinese Ministry of Education, Sun Yat-sen University , Guangzhou , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zhou","sequence":"additional","affiliation":[{"name":"Program in Immunology, Affiliated Guangzhou Women and Children\u2019s Medical Center, Zhongshan School of Medicine, Sun Yat-sen University , Guangzhou , China"},{"name":"Institute of Human Virology, Sun Yat-sen University , Guangzhou , China"},{"name":"Key Laboratory of Tropical Disease Control, Chinese Ministry of Education, Sun Yat-sen University , Guangzhou , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2016,2,26]]},"reference":[{"key":"2023011710415563400_B1","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1038\/nm.3160","article-title":"Fetomaternal immune cross-talk and its consequences for maternal and offspring\u2019s health","volume":"19","author":"Arck","year":"2013","journal-title":"Nat. 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