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 TH 1 response. We identified G protein-coupled receptor 55 (GPR55) as a potential target of miR-7116-5p, and miR-7116-5p promoted TH 1 cell function by downregulating GPR55. Moreover, GPR55 promoted MPE formation by inhibiting TH 1 cell expansion through the ERK phosphorylation pathway. These results uncover an IL-10-mediated pathway controlling TH 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.
journal_name
Eur J Immunoljournal_title
European journal of immunologyauthors
Zhai K,Shi XY,Yi FS,Huang ZY,Wu XZ,Dong SF,Wang W,Wu MT,Shi HZdoi
10.1002/eji.202048574subject
Has Abstractpub_date
2020-11-01 00:00:00pages
1798-1809issue
11eissn
0014-2980issn
1521-4141journal_volume
50pub_type
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