MicroRNA-9 Fine-Tunes Dendritic Cell Function by Suppressing Negative Regulators in a Cell-Type-Specific Manner

Abstract

Highlights d miR-9 promotes BMDC and cDC1 function d miR-9 expression suppresses negative regulators of DC function, including PCGF6 d miR-9 expressing cDC1s elicit greater antigen sensitivity in naive CD8 + T cells d miR-9 does not promote the activation or function of cDC2s

Cell‐intrinsic and ‐extrinsic roles of miRNAs in regulating T cell immunity

“…Overexpression of miR-9 in cDC2 does not lead to significant changes in the expression of costimulatory molecules and their capacity to activate T cells similar to what was observed in cDC1 with miR-9 overexpression. 91 Collectively, these results suggest that the distinct expression patterns and functions of miR-9 in different DC subtypes allow this miRNA to coordinately control DC responses to elicit appropriate T cell immunity. This study also offers a great example for understanding context-dependent and cell type-specific miRNA-mediated gene regulation within different immune cell subpopulations (Figure 2b).…”

“…89,90 Recently, another miRNA, miR-9, was also demonstrated to facilitate the maturation of DCs and enhance their function to stimulate T cell activation. 91 Interestingly, the positive effect of miR-9 on DCs was shown to be restricted to conventional DC1 (cDC1), a type of DCs that are particularly recognized for their role in eliciting antitumor immunity. 92 Upon activation, the expression of mature miR-9 is specifically upregulated in cDC1 but not cDC2.…”

Going ballistic: Leishmania nuclear subversion of host cell plasticity

“…Transcription factors (TFs) and microRNAs (miRNAs) constitute dynamic regulators of polarization and plasticity of monocytes, macrophages, and dendritic cells (DCs). The indicated TFs (A) and miRNAs (B) were previously linked to the two canonical subsets of polarized macrophages (M1, M2) and tumor-associated macrophages (TAMs)[6,35,[83][84][85][86][87][88][89][90] and the five types of dendritic cell subsets, that is, conventional DC1 and DC2 (cDC1 and cDC2)[91][92][93][94][95][96][97][98][99], monocyte-derived inflammatory DCs (moDCs)[100][101][102][103][104][105], skin-resident Langerhans cells (LCs)[106][107][108][109][110], and plasmacytoid DCs (pDCs)[79,91,107,[111][112][113][114][115][116]. An increase or decrease of miRNA abundance in these cells is indicated by, respectively, red and green fonts.…”

miR-aculous new avenues for cancer immunotherapy

“…miR-9 promotes cDC1 function and naïve CD8+ T-cell priming by repressing the transcriptional repressor polycomb group factor 6 (PCGF6). Further, DC miR-9 overexpression enhanced tumor clearance and the expansion of tumor-specific effector CD8+ T cells ( 155 , 156 ). Since the initial characterization of cDC1s, single-cell RNA sequencing has provided higher resolution of TADC subsets.…”