miR-146a regulates the homeostasis and function of CD11c + CD11b high dendritic cell subsets in mouse spleen
10.3760/cma.j.cn112309-20250407-00108
- VernacularTitle:miR-146a调控小鼠脾脏CD11c ＋CD11b high树突状细胞亚群稳态和功能
- Author:
Yi ZHANG
1
;
Jun ZHANG
1
;
Yingping XU
1
Author Information
1. 南方医科大学皮肤病医院皮肤病研究所，广州 510091
- Publication Type:Journal Article
- Keywords:
Dendritic cell;
miR-146a;
Toll-like receptor;
T cell proliferation;
Bone marrow-derived dendritic cell
- From:
Chinese Journal of Microbiology and Immunology
2025;45(7):570-577
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the regulatory role of miR-146a in the maintenance of homeostasis and function of conventional dendritic cells (cDCs).Methods:Bone marrow-derived dendritic cells (BMDCs) from wild-type (WT) and miR-146a knockout (miR-146a KO) mice were cultured in vitro. RT-PCR was used to analyze miR-146a expression in BMDCs stimulated by Toll-like receptor 4 (TLR4) ligand lipopolysaccharide (LPS) or TLR9 ligand CpG oligonucleotide (CpG-ODN); flow cytometry was performed to assess the expression of MHCⅡ and co-stimulatory markers (CD86 and CD80); RT-PCR and ELISA were used to measure the expression of cytokines at mRNA and protein levels, respectively; the influence of miR-146a-deficient BMDCs on CD4 + OTⅡT cell proliferation and differentiation was analyzed through in vitro co-culture and in vivo adoptive transfer experiments; flow cytometry was used to analyze the changes in the proportions of splenic DCs subsets in mice; the regulatory role of miR-146a in maintaining splenic DC homeostasis was further investigated using miR-146a KO mice and bone marrow chimeric models. Two-tailed t test was used for statistical analysis. Results:Following the stimulation with TLR4/9 ligands, miR-146a expression was significantly enhanced in BMDCs from WT mice ( P<0.01); the expression of MHCⅡ and CD86 in BMDCs from miR-146a KO mice were higher than in those from WT mice (all P<0.01). Following CpG-ODN stimulation, IL-12 and IL-6 expression at both mRNA and protein levels were higher in BMDCs from miR-146a KO mice than in those from WT mice (all P<0.05). However, no statistically significant differences in IL-12 or IL-6 expression were observed after LPS stimulation (all P>0.05). CpG-ODN-activated BMDCs demonstrated a robust capability to promote the proliferation of CD4 + OTⅡT cells and induced Th1/Th17 cell polarization (all P<0.01). Compared with WT mice, miR-146a KO mice showed a significant reduction in the CD11c + CD11b highcDC subsets in the spleen ( P<0.01). Bone marrow chimeric mice further confirmed that miR-146a played a critical role in maintaining the homeostasis of splenic CD11c + CD11b highcDC subsets. Conclusion:miR-146a regulates the homeostasis and function of cDC subsets, suggesting its potential for developing novel DC-based therapeutic strategies against microbial infections.
