MiR-16 regulates mouse peritoneal macrophage polarization and affects T-cell activation
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- 作者：Xiaoqin Jia ; Xiaomin Li ; Yating Shen ; Junjun Miao ; Hao Liu ; Guoli Li and Zhengbing Wang
- 刊名：Journal of Cellular and Molecular Medicine
- 出版年：2016
- 出版时间：October 2016
- 年：2016
- 卷：20
- 期：10
- 页码：1898-1907
- 全文大小：738K
- ISSN：1582-4934
文摘
MiR-16 is a tumour suppressor that is down-regulated in certain human cancers. However, little is known on its activity in other cell types. In this study, we examined the biological significance and underlying mechanisms of miR-16 on macrophage polarization and subsequent T-cell activation. Mouse peritoneal macrophages were isolated and induced to undergo either M1 polarization with 100 ng/ml of interferon-γ and 20 ng/ml of lipopolysaccharide, or M2 polarization with 20 ng/ml of interleukin (IL)-4. The identity of polarized macrophages was determined by profiling cell-surface markers by flow cytometry and cytokine production by ELISA. Macrophages were infected with lentivirus-expressing miR-16 to assess the effects of miR-16. Effects on macrophage–T cell interactions were analysed by co-culturing purified CD4+ T cells with miR-16-expressing peritoneal macrophages, and measuring activation marker CD69 by flow cytometry and cytokine secretion by ELISA. Bioinformatics analysis was applied to search for potential miR-16 targets and understand its underlying mechanisms. MiR-16-induced M1 differentiation of mouse peritoneal macrophages from either the basal M0- or M2-polarized state is indicated by the significant up-regulation of M1 marker CD16/32, repression of M2 marker CD206 and Dectin-1, and increased secretion of M1 cytokine IL-12 and nitric oxide. Consistently, miR-16-expressing macrophages stimulate the activation of purified CD4+ T cells. Mechanistically, miR-16 significantly down-regulates the expression of PD-L1, a critical immune suppressor that controls macrophage–T cell interaction and T-cell activation. MiR-16 plays an important role in shifting macrophage polarization from M2 to M1 status, and functionally activating CD4+ T cells. This effect is potentially mediated through the down-regulation of immune suppressor PD-L1.