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Publication : IL-10 promotes malignant pleural effusion by regulating T<sub>H</sub> 1 response via an miR-7116-5p/GPR55/ERK pathway in mice.

First Author  Zhai K Year  2020
Journal  Eur J Immunol Volume  50
Issue  11 Pages  1798-1809
PubMed ID  32506440 Mgi Jnum  J:298128
Mgi Id  MGI:6473054 Doi  10.1002/eji.202048574
Citation  Zhai K, et al. (2020) IL-10 promotes malignant pleural effusion by regulating TH 1 response via an miR-7116-5p/GPR55/ERK pathway in mice. Eur J Immunol 50(11):1798-1809
abstractText  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.
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