2. Academic Validation
  3. Kynurenine promotes the cytotoxicity of NK cells through aryl hydrocarbon receptor in early pregnancy

Kynurenine promotes the cytotoxicity of NK cells through aryl hydrocarbon receptor in early pregnancy

  • J Reprod Immunol. 2021 Feb:143:103270. doi: 10.1016/j.jri.2020.103270.
Shao-Liang Yang 1,  Hai-Xia Tan 2,  Tian-Tian Niu 3,  Da-Jin Li 4,  Hai-Yan Wang 5,  Ming-Qing Li 6
Affiliations

Affiliations

  • 1 Department of Gynecology of Integrated Traditional Chinese and Western Medicine, Hospital of Obstetrics and Gynecology, Fudan University, Shanghai, 200011, People's Republic of China; Laboratory for Reproductive Immunology, Hospital of Obstetrics and Gynecology, Fudan University, Shanghai, 200011, People's Republic of China.
  • 2 Department of Obstetrics and Gynecology, Zhangye People's Hospital of HeXi College, Zhangye, Gansu, 734000, People's Republic of China.
  • 3 Department of Gynecology of Integrated Traditional Chinese and Western Medicine, Hospital of Obstetrics and Gynecology, Fudan University, Shanghai, 200011, People's Republic of China.
  • 4 Laboratory for Reproductive Immunology, Hospital of Obstetrics and Gynecology, Fudan University, Shanghai, 200011, People's Republic of China; Key Laboratory of Reproduction Regulation of NPFPC, SIPPR, IRD, Fudan University, Shanghai, 200032, People's Republic of China.
  • 5 Department of Gynecology of Integrated Traditional Chinese and Western Medicine, Hospital of Obstetrics and Gynecology, Fudan University, Shanghai, 200011, People's Republic of China; Key Laboratory of Reproduction Regulation of NPFPC, SIPPR, IRD, Fudan University, Shanghai, 200032, People's Republic of China. Electronic address: [email protected].
  • 6 Laboratory for Reproductive Immunology, Hospital of Obstetrics and Gynecology, Fudan University, Shanghai, 200011, People's Republic of China; Key Laboratory of Reproduction Regulation of NPFPC, SIPPR, IRD, Fudan University, Shanghai, 200032, People's Republic of China; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, 200011, People's Republic of China. Electronic address: [email protected].
PMID: 33421663 DOI: 10.1016/j.jri.2020.103270
Abstract

During early pregnancy, decidual NK (dNK) cells play indispensable roles in many processes including the decidualization, the implantation, and the maintenance of immune tolerance. Abnormal cytotoxic activity of NK cells can cause recurrent spontaneous abortion (RSA), while the regulatory mechanism of NK cytotoxicity remains to be unclear. In this study, we found that kynurenine in decidua and villus was in a comparable level between patients with RSA and normal pregnancy women. However, the Aryl Hydrocarbon Receptor (AhR) in decidual NK cells was significantly increased in RSA. Compared with AhR- NK cells, cytotoxic activity-related molecules (NKP30, NKP46, NKG2D, perforin, granzyme B and IFN-γ) was highly expressed in both AhR+ peripheral and decidual NK cells, and kynurenine stimulation promoted the expression of killer receptors and the cytoplasmic granules in an AhR-dependent manner. Stimulation with TNF-α, IL-β and LPS upregulated the AhR expression in dNK cells in vitro. These results indicate that kyn/AhR signal enhances the cytotoxicity of NK cells, and increased expression of AhR may be an induction factor of RSA.

Keywords

Aryl hydrocarbon receptor; Kynurenine; NK cell; Pregnancy.

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