title: Decidual stromal cell-derived IL-33 contributes to Th2 bias and inhibits decidual NK cell cytotoxicity through NF-κB signaling in human early pregnancy.
abstract: Decidual stromal cells (DSCs) are an important component of decidual tissues where they are in strict proximity with immune cells. Although previous research has indicated that DSCs participate in the regulation of immune cells during pregnancy, the crosstalk between DSCs and decidual NK cells (dNKs) has not been fully elucidated. The aim of this study was to ascertain the effect of DSC-derived IL-33 on dNK function and explore the underlying mechanism. Flow cytometry showed a considerable increase in ST2 expression on dNKs compared with peripheral NKs (pNKs). Subsequent research found that perforin production, granzyme A production, and the cytolytic activity of dNKs were impaired by DSC media. Furthermore, the addition of DSC media induced an increase in Th2 cytokine production (IL-4, IL-13, and IL-10) with a concomitant decrease in Th1 cytokine expression (TNF-α) of dNKs. However, IFN-γ, another member of the Th1 cytokine family that is thought to be necessary during early gestation increased after IL-33 stimulation. DSC media sharply inhibited the expression of major activating receptors (NKp30, NKG2D) while up-regulating the levels of inhibitory receptor (KIR2DL1) on dNKs. The biological effect of DSC media on dNKs was abrogated by the administration of sST2. Moreover, Western blot analysis suggested that the NF-κB pathway was involved in the IL-33-induced changes in the phenotype and function of dNKs, which was further confirmed by pharmacological inhibition with the NF-κB inhibitor BAY 11-7082. Our results suggest that the crosstalk between DSCs and dNKs might play a crucial role in maintaining successful pregnancy.
authors.affiliation: Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Shanghai Medical College, Fudan University, Shanghai 200011, China.
authors.forename: Wen-Ting
authors.initials: WT
authors.lastname: Hu
authors.affiliation: Hospital of Integrated Traditional Chinese and Western Medicine, Baoshan District, Shanghai 201900, China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Huang
authors.affiliation: Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Shanghai Medical College, Fudan University, Shanghai 200011, China.
authors.forename: Ming-Qing
authors.initials: MQ
authors.lastname: Li
authors.affiliation: Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Shanghai Medical College, Fudan University, Shanghai 200011, China; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai 200011, China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Jin
authors.affiliation: Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Shanghai Medical College, Fudan University, Shanghai 200011, China.
authors.forename: Da-Jin
authors.initials: DJ
authors.lastname: Li
authors.affiliation: Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Shanghai Medical College, Fudan University, Shanghai 200011, China; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai 200011, China. Electronic address: zhuxiaoyong@fudan.edu.cn.
authors.forename: Xiao-Yong
authors.initials: XY
authors.lastname: Zhu
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D003656:Decidua / Q000166:cytology / Q000276:immunology*; D005260:Female; D006801:Humans; D000067596:Interleukin-33 / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D016328:NF-kappa B / Q000276:immunology*; D011247:Pregnancy / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D017154:Stromal Cells / Q000166:cytology / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*
chemical_list: C506536:IL33 protein, human; D000067596:Interleukin-33; D016328:NF-kappa B
keywords: Activating receptors; Cytolytic activity; Decidual NK cells; IL-33; Inhibitory receptors