2. Academic Validation
  3. Decidual RANKL/RANK interaction promotes the residence and polarization of TGF-β1-producing regulatory γδ T cells

Decidual RANKL/RANK interaction promotes the residence and polarization of TGF-β1-producing regulatory γδ T cells

  • Cell Death Dis. 2019 Feb 8;10(2):113. doi: 10.1038/s41419-019-1380-0.
Rui-Qi Chang 1,  Jun Shao 2,  Yu-Han Meng 3,  Jian Wang 1,  Da-Jin Li 4,  Ming-Qing Li 5 6
Affiliations

Affiliations

  • 1 Key Laboratory of Reproduction Regulation of NPFPC, SIPPR, IRD, Hospital of Obstetrics and Gynecology, Fudan University Shanghai Medical College, 200011, Shanghai, People's Republic of China.
  • 2 Department of Gynecology, Hospital of Obstetrics and Gynecology, Fudan University, 200011, Shanghai, People's Republic of China.
  • 3 Reproductive Medical Center, Affiliated Hospital of Weifang Medical University, 261030, Weifang, People's Republic of China.
  • 4 Key Laboratory of Reproduction Regulation of NPFPC, SIPPR, IRD, Hospital of Obstetrics and Gynecology, Fudan University Shanghai Medical College, 200011, Shanghai, People's Republic of China. dili@shmu.edu.cn.
  • 5 Key Laboratory of Reproduction Regulation of NPFPC, SIPPR, IRD, Hospital of Obstetrics and Gynecology, Fudan University Shanghai Medical College, 200011, Shanghai, People's Republic of China. mqli@fudan.edu.cn.
  • 6 Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Hospital of Obstetrics and Gynecology, Fudan University Shanghai Medical College, 200011, Shanghai, People's Republic of China. mqli@fudan.edu.cn.
PMID: 30737372 DOI: 10.1038/s41419-019-1380-0
Abstract

Decidual γδΤ (dγδΤ) cells play an essential role during successful pregnancy; however, the residence and polarization of γδΤ cells in decidua remain unclear. In this study, we observed higher levels of receptor activator for nuclear factor-κ B ligand (RANKL) on decidual stromal cells (DSCs), and its receptor RANK on dγδΤ cells in decidua from normal pregnancy compared with patients with recurrent spontaneous abortion (RSA). RANKL expressed by DSCs can induce the polarization of peripheral blood γδΤ (pγδΤ) and dγδΤ cells to Foxp3 + γδΤ cells, and upregulate the expression of transforming growth factor (TGF)-β1. This process is mediated through activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). In addition, RANKL promotes the adhesion of dγδΤ cells to DSCs in vitro, which is associated with the upregulation of ICAM-1 and VCAM-1 on DSCs and integrins on dγδΤ cells. RANKL knockout leads to the decreased numbers of uterus total γδΤ cells, Foxp3+γδΤ cells and the expression of TGF-β1, and the increased pregnancy loss in mice. These results suggest that RANKL is a pivotal regulator of maternal-fetal tolerance by triggering the polarization and residence of TGF-β1-producing Foxp3+γδΤ cells in early pregnancy. The abnormal low level of RANKL/RANK results in pregnancy loss because of the dialogue disorder between DSCs and dγδΤ cells. This observation provides a scientific basis on which a potential marker can be detected to early warning of pregnancy loss.

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