Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
Eur J Immunol. 2020 Nov;50(11):1798-1809. doi: 10.1002/eji.202048574. Epub 2020 Jun 26.
IL-10, produced by a wide variety of cells, is a highly pleiotropic cytokine that plays a critical role in the control of immune responses. However, its regulatory activity in tumor immunity remains poorly understood. In this study, we report that IL-10 deficiency robustly suppressed the formation of malignant pleural effusion (MPE) and significantly enhanced miR-7116-5p expression in pleural CD4 T cells. We demonstrated that miR-7116-5p suppressed IL-10-mediated MPE formation by inhibiting pleural vascular permeability as well as tumor angiogenesis and tumor growth. IL-10 promoted MPE formation by suppressing miR-7116-5p that enhances T 1 response. We identified G protein-coupled receptor 55 (GPR55) as a potential target of miR-7116-5p, and miR-7116-5p promoted T 1 cell function by downregulating GPR55. Moreover, GPR55 promoted MPE formation by inhibiting T 1 cell expansion through the ERK phosphorylation pathway. These results uncover an IL-10-mediated pathway controlling T 1 cells and demonstrate a central role for miR-7116-5p/GPR55/ERK signaling in the physiological regulation of IL-10-driven pro-malignant responses.
IL-10 是一种具有多种功能的细胞因子，它在控制免疫反应中起着关键作用。然而，其在肿瘤免疫中的调节作用仍知之甚少。在这项研究中，我们报告 IL-10 缺陷可强烈抑制恶性胸腔积液（MPE）的形成，并显著增强胸腔 CD4 T 细胞中的 miR-7116-5p 表达。我们证明 miR-7116-5p 通过抑制胸腔血管通透性以及肿瘤血管生成和肿瘤生长来抑制 IL-10 介导的 MPE 形成。IL-10 通过抑制 miR-7116-5p 来促进 MPE 形成，后者增强 T1 反应。我们确定 G 蛋白偶联受体 55（GPR55）是 miR-7116-5p 的潜在靶标，miR-7116-5p 通过下调 GPR55 来促进 T1 细胞功能。此外，GPR55 通过 ERK 磷酸化途径抑制 T1 细胞扩增来促进 MPE 形成。这些结果揭示了一种由 IL-10 介导的控制 T1 细胞的途径，并证明了 miR-7116-5p/GPR55/ERK 信号通路在生理调节 IL-10 驱动的促恶性反应中的核心作用。
