Differential Responses of Normal Human Melanocytes to Intra- and Extracellular dsRNA

Wang, Suiquan; Liu, Dongyin; Jin, Rong; Zhu, Yiping; Xu, Aie

doi:10.1089/dna.2014.2711

Cited by 10 publications

(7 citation statements)

References 44 publications

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“…The expression of β -ACTIN was found to be stable, and there was no significant difference in its expression with or without ligand stimulations (Figure S2C in Supplementary Material), verifying its suitability as a house-keeping gene for RT-qPCR normalization in this study. The differential responses to intra- and extracellular stimulation of poly(I:C) has been reported, with a 1,000- to 10,000-fold increase for intracellular transfection ( 27 , 28 ). These data suggest that sensing of poly(I:C) by TLR10 likely occurs in intracellular compartments and to certain extent in accordance with the abundant expression of TLR10 found intracellularly compared with that on the cell surface.…”

Section: Resultsmentioning

confidence: 99%

Recognition of Double-Stranded RNA and Regulation of Interferon Pathway by Toll-Like Receptor 10

et al. 2018

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Toll-like receptor (TLR)-10 remains an orphan receptor without well-characterized ligands or functions. Here, we reveal that TLR10 is predominantly localized to endosomes and binds dsRNA in vitro at endosomal pH, suggesting that dsRNA is a ligand of TLR10. Recognition of dsRNA by TLR10 activates recruitment of myeloid differentiation primary response gene 88 for signal transduction and suppression of interferon regulatory factor-7 dependent type I IFN production. We also demonstrate crosstalk between TLR10 and TLR3, as they compete with each other for dsRNA binding. Our results suggest for the first time that dsRNA is a ligand for TLR10 and propose novel dual functions of TLR10 in regulating IFN signaling: first, recognition of dsRNA as a nucleotide-sensing receptor and second, sequestration of dsRNA from TLR3 to inhibit TLR3 signaling in response to dsRNA stimulation.

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Section: Resultsmentioning

confidence: 99%

Recognition of Double-Stranded RNA and Regulation of Interferon Pathway by Toll-Like Receptor 10

et al. 2018

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“…Mx1 can cause hindrance in replication of RNA and DNA viruses 28 . In fact, several studies have linked the pathogenesis of vitiligo to the infection of a variety of viruses, such as cytomegalovirus, hepatitis virus, and HIV 29 , but the exact mechanism of viral infection leading to vitiligo has not been fully elucidated. MX1 may provide a new research target for vitiligo development.…”

Section: Discussionmentioning

confidence: 99%

Integrative Analysis to Identify Diagnostic Biomarkers (HSP90AA1, VCAM1 and MX1) and Reveal Immune Cell Infiltration Changes in Patients with Vitiligo

Huang

Fan

et al. 2022

Preprint

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Background This current study applied bioinformatics analysis to reveal the potential role of immune-related genes and blood immune cell infiltration changes in vitiligo development. Methods The gene expression level was obtained from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified between blood samples from patients with segmental vitiligo (SV), non-segmental vitiligo (NSV) and healthy controls (CL), and the DEGS from two sets were used for further analysis respectively, including hub gene exploration, enrichment analysis, interaction network construction and engaged pathway analysis. Immune-related gene crosstalk analysis, gene-miRNA analysis, and AUC analysis were performed for further gene screening. Furthermore, immune cell infiltration analysis was also performed to reveal the change of systemic environment in patients with vitiligo. Results There were 161 DEGs in the comparison of SV and CL, 11 DEGs in NSV and CL. Functional enrichment analysis indicated that DEGS in NSV group mainly involved in responses to virus and type 1 interferon signaling pathway, while DEGS in SV group mainly involved in IL-17 signaling pathway and TNF signaling pathway. After PPI network construction, immune-related gene crosstalk analysis, and verification of diagnostic markers, totally 4 genes were obtained as diagnostic markers (VCAM1, HSP90AA1, TNF from SV group and MX1 from NSV group). Moreover, we found that the infiltrated percentage of resting memory CD4 T cells were both higher in blood samples from patients with segmental vitiligo and non-segmental vitiligo. Conclusion For the first time, VCAM1, HSP90AA1, and MX1 were found associated with vitiligo and had good diagnostic significance. Meanwhile, we found that vitiligo patients had more proportion of resting memory CD4 T cells infiltration in blood. These results may provide new research ideas for the pathogenesis and diagnosis of vitiligo.

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“…Notably, previous studies also emphasized the roles of IFN-β in reinforcing and bridging the innate and adaptive immunology such as promoting dendritic cells (DCs) maturation, skewing of TH1 polarization and reactivation of CTLs (cytotoxic T lymphocyte) 41,66 . Besides, MDA5 belongs to the RIG-I-like receptor family (RLR family) which could initiate the production of pro-inflammatory factors including IL-6, IL-8, IL-23, and TNF-α 31,67,68 . Hence, whether other functions of MDA5 participate in the pathogenesis of vitiligo in response to virus invasion is worthy to be explored.…”

Section: Discussionmentioning

confidence: 99%

Intracellular virus sensor MDA5 exacerbates vitiligo by inducing the secretion of chemokines in keratinocytes under virus invasion

Zhuang

Chen

et al. 2020

Cell Death Dis

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Vitiligo is a disfiguring disease featuring chemokines-mediated cutaneous infiltration of autoreactive CD8 + T cells that kill melanocytes. Copious studies have indicated that virus invasion participates in the pathogenesis of vitiligo. IFIH1, encoding MDA5 which is an intracellular virus sensor, has been identified as a vitiligo susceptibility gene. However, the specific role of MDA5 in melanocyte death under virus invasion is not clear. In this study, we first showed that the expression of anti-CMV IgM and MDA5 was higher in vitiligo patients than healthy controls. Then, by using Poly(I:C) to imitate virus invasion, we clarified that virus invasion significantly activated MDA5 and further potentiated the keratinocyte-derived CXCL10 and CXCL16 which are the two vital chemokines for the cutaneous infiltration of CD8 + T cells in vitiligo. More importantly, IFN-β mediated by the MDA5-MAVS-NF-κB/IRF3 signaling pathway orchestrated the secretion of CXCL10 via the JAK1-STAT1 pathway and MDA5-meidiated IRF3 transcriptionally induced the production of CXCL16 in keratinocytes under virus invasion. In summary, our results demonstrate that MDA5 signaling orchestrates the aberrant skin immunity engaging in melanocyte death via mediating CXCL10 and CXCL16 secretion, which supports MDA5 as a potential therapeutic target for vitiligo under virus invasion.

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Differential Responses of Normal Human Melanocytes to Intra- and Extracellular dsRNA

Cited by 10 publications

References 44 publications

Recognition of Double-Stranded RNA and Regulation of Interferon Pathway by Toll-Like Receptor 10

Recognition of Double-Stranded RNA and Regulation of Interferon Pathway by Toll-Like Receptor 10

Integrative Analysis to Identify Diagnostic Biomarkers (HSP90AA1, VCAM1 and MX1) and Reveal Immune Cell Infiltration Changes in Patients with Vitiligo

Intracellular virus sensor MDA5 exacerbates vitiligo by inducing the secretion of chemokines in keratinocytes under virus invasion

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