Decidual NR2F2-Expressing CD4+ T Cells Promote TH2 Transcriptional Program During Early Pregnancy
A unique immunotolerant microenvironment with Th2 bias in the decidua provides an essential security for successful pregnancy. The disorganized maternal-fetal immune tolerance contributes to more than 50% of unexplained recurrent spontaneous abortion (RSA). How the Th2 bias is developed at the mater...
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Published in | Frontiers in immunology Vol. 12; p. 670777 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
Frontiers Media S.A
18.05.2021
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Subjects | |
Online Access | Get full text |
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Summary: | A unique immunotolerant microenvironment with Th2 bias in the decidua provides an essential security for successful pregnancy. The disorganized maternal-fetal immune tolerance contributes to more than 50% of unexplained recurrent spontaneous abortion (RSA). How the Th2 bias is developed at the maternal-fetal interface remains undefined. NR2F2, a member of steroid/thyroid nuclear receptor superfamily, is endowed with diverse importance in cell-fate specification, organogenesis, angiogenesis, and metabolism. Here, we showed that NR2F2 was absolutely highly expressed in decidual CD4
+
T(dCD4
+
T) cells, but not in peripheral circulating CD4
+
T cells during early pregnancy. Decidual NR2F2-expressing CD4
+
T cells dominantly produced Th2 cytokines. In unexplained RSA patients, NR2F2 expression in dCD4
+
T cells was significantly decreased, accompanied with disordered phenotype of dCD4
+
T cells. Furthermore, overexpression of NR2F2 promoted the Th2 differentiation of naive CD4
+
T cells. Immunoprecipitation experiment confirmed the binding relationship between GATA-3 and NR2F2, which implied GATA-3 may be an important interactive element involved in the immunoregulatory process of NR2F2. This study is the first to reveal a previously unappreciated role for NR2F2-mediated dCD4
+
T cells in maternal-fetal immune tolerance and maintenance of normal pregnancy, in the hope of providing a potential biomarker for prediction and prevention of clinical unexplained RSA. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 This article was submitted to Immunological Tolerance and Regulation, a section of the journal Frontiers in Immunology Edited by: Sha Wu, Southern Medical University, China These authors have contributed equally to this work Reviewed by: Binqing Fu, University of Science and Technology of China, China; Haiming Wei, University of Science and Technology of China, China; Yafei Huang, Huazhong University of Science and Technology, China |
ISSN: | 1664-3224 1664-3224 |
DOI: | 10.3389/fimmu.2021.670777 |