穿孔素
颗粒酶B
间质细胞
生物
白细胞介素12
流式细胞术
免疫学
CD16
自然杀伤细胞
细胞因子
受体
白细胞介素15
分子生物学
细胞生物学
白细胞介素
T细胞
免疫系统
癌症研究
细胞毒性T细胞
CD3型
体外
CD8型
生物化学
作者
Hui‐Li Yang,Wen‐Jie Zhou,Han Lü,Shating Lei,Si‐Yao Ha,Zhen‐Zhen Lai,Zimeng Zheng,Lu‐Yu Ruan,Yongzhong He,Da‐Jin Li,Ming‐Qing Li,Jun Shao
摘要
Problem Decidual stromal cells (DSCs) are important origins of cytokines to modulate maternal‐fetal immunotolerance and provide a feasible environment for embryo implantation and development. Interleukin (IL)‐24 is a multifunctional cancer killing cytokine and a pleiotropic immunoregulator with complex potency according to tissue or cell types. Its role in establishment and maintenance of normal pregnancy is largely unknown. The aim of our study was to investigate the function and significance of IL‐24 and its receptor in the coordination between DSCs and natural killer cells (NK) in early pregnancy. Method of study The levels of IL‐24 in DSC, endometrial stromal cell (ESC), peripheral blood NK cells (pNK), or decidual NK cells (dNK) culture supernatants were detected by enzyme‐linked immunosorbent assay (ELISA), and the levels of IL‐24 receptors were determined by real‐time reverse transcriptase‐polymerase chain reaction (RT‐PCR) and flow cytometry assays. The effect of IL‐24 on the functions of decidual NK cells was analyzed by flow cytometry assays in vitro. Results The concentration of IL‐24 in culture supernatant of DSCs was significantly higher than that of ESCs. Both eNK (endometrial NK cells) and dNK highly expressed IL‐24 receptors (IL‐20R1 and IL‐22R1), especially on CD56 dim eNK. However, there were extremely low levels of IL‐20R1 and IL‐22R1 on pNK. Recombinant human IL‐24 or DSCs‐secreted IL‐24 downregulated the levels of CD16, Granzyme B, perforin, and interferon (IFN)‐γ and upregulated the levels of inhibitory receptors killer‐cell immunoglobulin‐like receptor (KIR)2DL1 and KIR3DL1, or immunotolerant or angiogenic cytokines (eg, transforming growth factor (TGF)‐β, IL‐10, and IL‐8), and elevated the percentage of CD56 bright CD16 − dNK in vitro. Conclusion These data suggest that DSCs promote the differentiation of CD56 bright CD16 − NK with high levels of inhibitory receptors, immunotolerant, and angiogenic cytokines by secreting IL‐24 during decidualization in early pregnancy.
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