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精氨酸酶1阳性2型固有淋巴细胞和固有淋巴细胞调节细胞在妊娠期糖尿病进展中的作用。

Role of Arg1 ILC2s and ILCregs in gestational diabetes progression.

作者信息

Gong Zhangyun, Yi Haixing, Zhang Jie, Li Wan, Wang Hao, Guo Peipei, Li Caihua, Pan Anan, Cao Yunxia, Lu Zhimin, Jiang Huanhuan

机构信息

Department of Obstetrics and Gynecology, Reproductive Medicine Center, The First Affiliated Hospital of Anhui Medical University, Wanshui Road No. 120, Hefei, 230000, Anhui, China.

NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, No 81 Meishan Road, Hefei, 230032, Anhui, China.

出版信息

Sci Rep. 2025 Jan 10;15(1):1580. doi: 10.1038/s41598-025-85452-x.

Abstract

Innate lymphoid cells (ILCs) are a newly discovered subset of immune cells that are responsible for regulation of the immune microenvironment. In particular, the ILC categories ILC2s and regulatory ILCs (ILCregs) are associated with immunosuppression and chronic inflammation. Chronic low-grade inflammation leads to insulin resistance, a major etiological factor in gestational diabetes mellitus (GDM). However, the influence of ILCs on GDM remains poorly understood. Therefore, this study aims to investigate the potential role of ILCs in the development and progression of GDM. This study included 19 patients diagnosed with GDM and 19 age- and body mass index-matched individuals in the control group. Flow cytometry was employed to assess the frequency and function of ILC subsets in peripheral blood (PB), cord blood (CB), and placental tissues. Additionally, ELISA was utilized to measure the levels of the cytokines TNF-α, IFN-γ, TGF-β, and IL-4/10/13/22 in the serum samples of patients. Compared to the control group with normal pregnancy, significantly elevated levels of ILC2s, Arg1ILC2s, and ILCregs were detected in the PB, CB, and placental tissues of the GDM group. With regard to inflammation-related cytokines, the levels of IL-13/22 in PB serum were significantly elevated, while the TGF-β levels were significantly reduced in the GDM group compared to the control group (CG). Further, in the CB serum samples, IL-13 levels were elevated in the GDM group. Additionally, a negative correlation was observed between the number of ILC3s and the number of ILCregs present in umbilical cord blood, while the IL-13 level in peripheral blood was negatively correlated with the number of ILC3s. The present findings indicate that chronic low-grade inflammation mediated by Arg-1ILC2s and ILCregs is closely associated with the pathogenesis of GDM.

摘要

固有淋巴细胞(ILCs)是新发现的一类免疫细胞亚群,负责调节免疫微环境。特别是,ILC2亚群和调节性ILCs(ILCregs)与免疫抑制和慢性炎症相关。慢性低度炎症会导致胰岛素抵抗,这是妊娠期糖尿病(GDM)的一个主要病因。然而,ILCs对GDM的影响仍知之甚少。因此,本研究旨在探讨ILCs在GDM发生发展中的潜在作用。本研究纳入了19例诊断为GDM的患者和19例年龄及体重指数相匹配的对照组个体。采用流式细胞术评估外周血(PB)、脐血(CB)和胎盘组织中ILC亚群的频率和功能。此外,利用酶联免疫吸附测定(ELISA)检测患者血清样本中细胞因子TNF-α、IFN-γ、TGF-β和IL-4/10/13/22的水平。与正常妊娠的对照组相比,在GDM组的PB、CB和胎盘组织中检测到ILC2s、精氨酸酶1阳性ILC2s(Arg1ILC2s)和ILCregs水平显著升高。关于炎症相关细胞因子,与对照组(CG)相比,GDM组PB血清中IL-13/22水平显著升高,而TGF-β水平显著降低。此外,在CB血清样本中,GDM组IL-13水平升高。此外,观察到脐血中ILC3s数量与ILCregs数量呈负相关,而外周血中IL-13水平与ILC3s数量呈负相关。目前的研究结果表明,由Arg-1ILC2s和ILCregs介导的慢性低度炎症与GDM的发病机制密切相关。

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