Regulation of innate immune response by miRNAs up-regulated in Stevens-Johnson syndrome with severe ocular complications
Abstract Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe mucocutaneous disorders characterized by extensive tissue necrosis; they are often accompanied by severe ocular complications (SOC). The regulatory role of microRNAs (miRNAs) in modulating immune responses in SJS...
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Nature Portfolio
2025-01-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-85528-8 |
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| author | Mayumi Ueta Hiromi Nishigaki Hokoru Yoshioka Shigeru Kinoshita Chie Sotozono |
| author_facet | Mayumi Ueta Hiromi Nishigaki Hokoru Yoshioka Shigeru Kinoshita Chie Sotozono |
| author_sort | Mayumi Ueta |
| collection | DOAJ |
| description | Abstract Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe mucocutaneous disorders characterized by extensive tissue necrosis; they are often accompanied by severe ocular complications (SOC). The regulatory role of microRNAs (miRNAs) in modulating immune responses in SJS/TEN is not fully understood, particularly in relation to chronic SOC. We explored the expression profiles of specific miRNAs and their potential impact on the regulation of key innate immune genes in patients with SJS/TEN with SOC. We analyzed plasma samples from 100 patients with chronic stage SJS/TEN with SOC and 92 healthy controls to examine the expression levels of eight specific miRNAs (let-7a-5p, let-7d-3p, let-7e-5p, miR-146a-5p, miR-130a-3p, miR-151a-3p, miR-151a-5p, miR-27b-3p) using quantitative RT-PCR (RT-qPCR). In addition, we subjected mononuclear cells from 12 SJS/TEN patients and 9 controls to RT-qPCR to assess the expression of the innate immune-related genes IFI44L, TNFSF10, AIM2, RSAD2, CXCL10, TRIM22, IFI27, and IFIT2. Significant upregulation of 4 miRNAs (let-7a-5p, let-7e-5p, miR-146a-5p, and miR-27b-3p) was observed in the plasma of SJS/TEN patients; this correlated with the increased expression of TLR3, RIG-I, and MDA5. Furthermore, MDA5, IFI44L, RSAD2, CXCL10, and IFIT2 were also significantly up-regulated in the mononuclear cells from these patients, indicating a systemic modulation of immune response genes. Our findings demonstrate that specific miRNAs are up-regulated in SJS/TEN with SOC and associated with the upregulation of critical immune response genes, suggesting their involvement in the pathogenesis and persistence of SOC. These miRNAs and their target genes may serve as potential biomarkers or therapeutic targets in managing SJS/TEN with SOC. |
| format | Article |
| id | doaj-art-6ef13ff75f2a4d2c8484d9372065e9ec |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-6ef13ff75f2a4d2c8484d9372065e9ec2025-01-12T12:17:25ZengNature PortfolioScientific Reports2045-23222025-01-0115111010.1038/s41598-025-85528-8Regulation of innate immune response by miRNAs up-regulated in Stevens-Johnson syndrome with severe ocular complicationsMayumi Ueta0Hiromi Nishigaki1Hokoru Yoshioka2Shigeru Kinoshita3Chie Sotozono4Department of Ophthalmology, Kyoto Prefectural University of MedicineDepartment of Ophthalmology, Kyoto Prefectural University of MedicineDepartment of Ophthalmology, Kyoto Prefectural University of MedicineDepartment of Ophthalmology, Kyoto Prefectural University of MedicineDepartment of Ophthalmology, Kyoto Prefectural University of MedicineAbstract Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe mucocutaneous disorders characterized by extensive tissue necrosis; they are often accompanied by severe ocular complications (SOC). The regulatory role of microRNAs (miRNAs) in modulating immune responses in SJS/TEN is not fully understood, particularly in relation to chronic SOC. We explored the expression profiles of specific miRNAs and their potential impact on the regulation of key innate immune genes in patients with SJS/TEN with SOC. We analyzed plasma samples from 100 patients with chronic stage SJS/TEN with SOC and 92 healthy controls to examine the expression levels of eight specific miRNAs (let-7a-5p, let-7d-3p, let-7e-5p, miR-146a-5p, miR-130a-3p, miR-151a-3p, miR-151a-5p, miR-27b-3p) using quantitative RT-PCR (RT-qPCR). In addition, we subjected mononuclear cells from 12 SJS/TEN patients and 9 controls to RT-qPCR to assess the expression of the innate immune-related genes IFI44L, TNFSF10, AIM2, RSAD2, CXCL10, TRIM22, IFI27, and IFIT2. Significant upregulation of 4 miRNAs (let-7a-5p, let-7e-5p, miR-146a-5p, and miR-27b-3p) was observed in the plasma of SJS/TEN patients; this correlated with the increased expression of TLR3, RIG-I, and MDA5. Furthermore, MDA5, IFI44L, RSAD2, CXCL10, and IFIT2 were also significantly up-regulated in the mononuclear cells from these patients, indicating a systemic modulation of immune response genes. Our findings demonstrate that specific miRNAs are up-regulated in SJS/TEN with SOC and associated with the upregulation of critical immune response genes, suggesting their involvement in the pathogenesis and persistence of SOC. These miRNAs and their target genes may serve as potential biomarkers or therapeutic targets in managing SJS/TEN with SOC.https://doi.org/10.1038/s41598-025-85528-8Stevens-Johnson syndromemiRNAsPlasmaInnate immunitySevere ocular complications |
| spellingShingle | Mayumi Ueta Hiromi Nishigaki Hokoru Yoshioka Shigeru Kinoshita Chie Sotozono Regulation of innate immune response by miRNAs up-regulated in Stevens-Johnson syndrome with severe ocular complications Scientific Reports Stevens-Johnson syndrome miRNAs Plasma Innate immunity Severe ocular complications |
| title | Regulation of innate immune response by miRNAs up-regulated in Stevens-Johnson syndrome with severe ocular complications |
| title_full | Regulation of innate immune response by miRNAs up-regulated in Stevens-Johnson syndrome with severe ocular complications |
| title_fullStr | Regulation of innate immune response by miRNAs up-regulated in Stevens-Johnson syndrome with severe ocular complications |
| title_full_unstemmed | Regulation of innate immune response by miRNAs up-regulated in Stevens-Johnson syndrome with severe ocular complications |
| title_short | Regulation of innate immune response by miRNAs up-regulated in Stevens-Johnson syndrome with severe ocular complications |
| title_sort | regulation of innate immune response by mirnas up regulated in stevens johnson syndrome with severe ocular complications |
| topic | Stevens-Johnson syndrome miRNAs Plasma Innate immunity Severe ocular complications |
| url | https://doi.org/10.1038/s41598-025-85528-8 |
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