IL‐10 promotes malignant pleural effusion by regulating TH1 response via an miR‐7116‐5p/GPR55/ERK pathway in mice

Abstract 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.