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  • br Conclusion br Conflict of

    2023-01-16


    Conclusion
    Conflict of interest
    Acknowledgments We thank Nancy Kerkvliet for helpful advice. The research in the lab of CE and THS is supported by the Deutsche Forschungsgemeinschaft (grants ES103/7-1 and 9-1, HA7346/2-1). We apologize to all authors whose work could not be cited due to limitation of space.
    Introduction Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a chronic heterogeneous disease of epithelial inflammation and tissue eosinophilic infiltration [1,2]. In patients with nasal polyposis (NPs), the nasal mucosal epithelium is histologically characterized by persistent inflammation and irreversible structural changes, which leads to remodeling in the nasal mucosal [3]. Although there are many studies on the role of chronic inflammation in the development of nasal polyps, but the underlying mechanism is still not clear. The aryl hydrocarbon receptor (AHR) is a member of the basic helix-loop-helix Per-Arnt-Sim (bHLH-PAS) transcription factor family. In previous studies, some chemicals or xenobiotics can respond to the immune response by mediating AHR [[4], [5], [6]]. In the immune system, it is well known that the A-317491 of AHR needs to be tightly controlled, aberrant expression of AHR can cause system disorders [[7], [8], [9], [10]]. AHR activation can facilitate the generation of Treg or Th17 cells based on the disease model, tissue context and type of AHR ligand, then directly influencing the Th17/Treg balance [[11], [12], [13]]. AHR plays a very important role in inflammation and immune response, and it is involved in the regulation of a variety of signaling pathways. MicroRNAs (miRNAs) are noncoding transcripts of 18–25 nucleotides (nts) derived from initially long primary transcripts. mature miRNAs can specifically bind to 3′-untranslated regions (3′-UTRs) of target mRNAs, leading to either mRNA degradation or inhibition of translation [11]. We used quantitative PCR to determine the expression of a series of inflammation-associated miRNAs in the nasal mucosa of CRSwNPs. It was found that the expression of miR124 was most significantly reduced in CRSwNPs in nasal mucosa, which attracted us enough attention [Fig. S1]. According to TargetScan analysis, AHR 3′-UTR contains the binding site of the miR-124/124ab family and is highly conserved among humans, mice and most species. Research has shown that miR124 is one of the most abundantly expressed miRNAs in the nervous system and it is also highly expressed in the immune cells and organs [[12], [13], [14]]. MiR124 can inactivate macrophages, thereby promoting microglial quiescence and inhibiting experimental autoimmune encephalomyelitis (EAE) [15]. And miR124 inhibits the differentiation of TH1 and TH17 cells by inhibiting STAT1 and STAT3 activation in the presence of protein inhibitor cytokine signaling 5 (SOCS5) [16]. In our study, we found that the expression of miR124 is reduced in NPs, which prompts us to investigate the relationship between miR124 and inflammation in NPs. In the present study, our results demonstrated that miR124 can negatively regulate the expression of AHR and inflammatory cytokine, and inhibition of AHR expression results in loss of miR124 regulating inflammatory factors. This study has identified that Micro124-mediated AHR expression regulates the inflammatory response of chronic rhinosinusitis (CRS) with nasal polyps, and which acts as a novel essential regulator of inflammatory response. In future miR124/AHR pathway may be acted as a new therapeutic target and clinical strategies to modulate inflammation-related diseases.
    Materials and methods
    Results
    Discussion The aryl hydrocarbon receptor (AHR) is a ligand-inducible transcription factor that is an important component of the host's response to environmental stimuli, which is essential for modulating the immune response [17,18]. There are many signaling pathways about AHR, but are few reported on the regulation of AHR by miRNAs. In our study, AHR is significantly higher in nasal polyps compared to normal tissues, and there was an inverse correlation with the expression changes of miR124. We change the expression of miR124 that can affect the expression of AHR and the secretion of inflammatory factors, but which can be saved by interfering the expression of AHR. The above evidence suggests that miR124 may regulate the body's inflammatory response through regulating the expression of AHR.