Abstract
The Cytosine–phosphate–guanosine (CpG) motif, which is specifically recognized intracellularly by dendritic cells (DCs), plays a crucial role in regulating the innate immune response. MicroRNAs (miRNAs) can strongly influence the antigen-presenting ability of DCs. In this study, we examine the action of miRNAs on CpG-stimulated and control DCs, as well as their effect on cyclic guanosine monophosphate-adenosine monophosphate (GMP–AMP) synthase (cGAS) and the stimulator of interferon genes (STING) signal pathway. Firstly, we selected miRNAs (miR-29a and miR-378b) based on expression in CpG-stimulated mouse bone marrow-derived dendritic cells (BMDCs). Secondly, we investigated the functions of miR-29a and miR-378b on CpG-stimulated and unstimulated BMDCs. The results showed that miR-29a and miR-378b increased expression of both the immunoregulatory DC surface markers (CD86 and CD40) and the immunosuppressive molecule CD273 by DCs. Thirdly, cytokine detection revealed that both miR-29a and miR-378b enhanced interferon-β (IFN-β) expression while suppressing tumor necrosis factor-α (TNF-α) production. Finally, our results suggest that miR-378b can bind TANK-binding kinase binding protein 1 (TBKBP1) to activate the cGAS/STING signaling pathway. By contrast, miR-29a targeted interferon regulatory factor 7 (IRF7) and promoted the expression of STING. Together, our results provide insight into the molecular mechanism of miRNA induction by CpG to regulate DC function.
Highlights
Dendritic cells (DCs) are the most important antigen-presenting cells (APCs) [1]
We focused on CpG-stimulated dendritic cells (DCs) maturation and identification of the miRNAs that may influence CpG activity in bone marrow-derived dendritic cells (BMDCs)
To confirm the previously obtained microarray data, we examined the expression of six miRNAs listed above, which were stimulated by CpG in mouse BMDCs. qPCR results showed that all miRNAs exhibited peak expression at 48 h, while miR-29a and miR-378b showed continuous increases in significance over various time intervals (Figure 1C)
Summary
The ability of DCs to present antigens and initiate an immune response forms a link between the innate and the acquired immune system. This process is known as DC maturation, which is characterized by upregulating major histocompatibility complex class II (MHCII) and co-stimulatory molecules (CD80, CD86, and CD40). Unlike co-stimulatory molecules, DCs can be negatively regulated by recognition of co-inhibitory molecules (sialic-acid-binding immunoglobulin-like lectin-G (Siglec-G) and CD273), containing an immunoreceptor tyrosine-based inhibitory motif (ITIM). Siglec-G, a member of the Siglec family, contains ITIM intracellularly [2]. As a member of the immunoglobulin (Ig) superfamily, CD273 contains ITIM in its cytoplasmic tail [3]
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