IL-10 promotes malignant pleural effusion by regulating T_H 1 response via an miR-7116-5p/GPR55/ERK pathway in mice

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_H 1 response. We identified G protein-coupled receptor 55 (GPR55) as a potential target of miR-7116-5p, and miR-7116-5p promoted T_H 1 cell function by downregulating GPR55. Moreover, GPR55 promoted MPE formation by inhibiting T_H 1 cell expansion through the ERK phosphorylation pathway. These results uncover an IL-10-mediated pathway controlling T_H 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.