716630d0452824e6293d9410d6761b35 pmc_33801296.pdf fc6a2db9d9270f92f443fba1a039a4f0b84356af pmc_33801296.pdf 98a681e481a83efacf49b1d42a2055d8b426174dcda3944553e9c238198d960f pmc_33801296.pdf Title: The Expression of IL-17, in Chronic Spontaneous Urticaria Is Linked to Semaphorin5A Subject: Background: Patients with chronic spontaneous urticaria (CSU), an autoimmune disorder, show increased skin expression of IL-17A and can benefit from treatment with the anti-IL-17A biologic secukinumab. The mechanisms that drive IL-17A expression in CSU are currently unknown, but may involve Semaphorin5A (Sema5A). Objective: To explore the expression, role, and effects of Sema5A in CSU and its link to IL-17A. Material and Methods: We investigated patients with CSU and healthy controls for skin expression of expressing peripheral T cells. Results: Sema5A was highly expressed in the skin of CSU patients as compared to healthy control skin. Both CD4+ T cells and mast cells in CSU skin expressed Sema5A, and many of them expressed both Sema5A and IL-17A. Patients with CSU had significantly higher rates of IL-17A-expressing CD4+ T cells as compared to healthy controls. Incubation with Sema5A increased the rates of IL-17A-expressing CD4+ T cells in healthy controls to CSU levels. Conclusion: Sema5A may drive the expression and effects of IL-17A in CSU. Further studies in larger cohorts are needed to confirm the role of Sema5A in the pathogenesis of CSU and to explore its potential as a therapeutic target. Keywords: chronic spontaneous urticaria; T cells; mast cells; semaphorin5A; IL-17 Author: Matanis Lobna, Eiza Nasren, Sabag Adi, Bejar Jacob, Gimenez-Arnau Ana Maria, Maurer Marcus and Vadasz Zahava Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Fri Mar 12 08:29:01 2021 CET ModDate: Fri Mar 12 08:35:42 2021 CET Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 7 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 3313302 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- NUNBCL+URWPalladioL-Ital Type 1 Custom yes yes no 10 0 AMNUCG+URWPalladioL-Bold Type 1 Custom yes yes no 15 0 SZMGFL+URWPalladioL-Roma Type 1 Custom yes yes no 19 0 XKSBAY+EURM10 Type 1 Builtin yes yes no 23 0 IVVSWS+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 33 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 63 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 67 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 71 0 HYUQZR+TeX-tipa10 Type 1 Builtin yes yes no 83 0 VYVZGZ+CMSY10 Type 1 Builtin yes yes no 90 0 PFFLOH+PalatinoLinotype TrueType WinAnsi yes yes no 101 0 PFFMCH+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 104 0 PFFMDJ+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 107 0 PFFLOH+PalatinoLinotype TrueType WinAnsi yes yes no 122 0 PFFMCH+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 125 0 PFFMDJ+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 128 0 PFFLOH+PalatinoLinotype TrueType WinAnsi yes yes no 140 0 PFFMCH+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 143 0 PFFMDJ+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 146 0 PFFLOH+PalatinoLinotype TrueType WinAnsi yes yes no 161 0 PFFMCH+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 164 0 PFFMDJ+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 167 0 PFFLOH+PalatinoLinotype TrueType WinAnsi yes yes no 179 0 PFFMCH+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 182 0 PFFMDJ+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 185 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-10-02 03:25:30 CEST RepresentationInformation: pmc_33801296.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2023-03-31 12:09:24 CEST Size: 3313302 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 271 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Material and Methods Destination: section.2 Children: Item: Title: Study Subjects and Ethical Considerations Destination: subsection.2.1 Item: Title: Immunohistochemistry Destination: subsection.2.2 Item: Title: Peripheral Activated CD4+ T Cell Assays Destination: subsection.2.3 Item: Title: Statistical Analysis Destination: subsection.2.4 Item: Title: Results Destination: section.3 Children: Item: Title: Many CD4+ T Cells and Mast Cells in the Skin of CSU Patients Express Sema5A and IL-17A Destination: subsection.3.1 Item: Title: Sema5A Increases IL-17A Expression in Peripheral CD4+ T Cells Destination: subsection.3.2 Item: Title: Discussion Destination: section.4 Item: Title: References Destination: section.4 Info: Title: The Expression of IL-17, in Chronic Spontaneous Urticaria Is Linked to Semaphorin5A Author: Matanis Lobna, Eiza Nasren, Sabag Adi, Bejar Jacob, Gimenez-Arnau Ana Maria, Maurer Marcus and Vadasz Zahava Subject: Background: Patients with chronic spontaneous urticaria (CSU), an autoimmune disorder, show increased skin expression of IL-17A and can benefit from treatment with the anti-IL-17A biologic secukinumab. The mechanisms that drive IL-17A expression in CSU are currently unknown, but may involve Semaphorin5A (Sema5A). Objective: To explore the expression, role, and effects of Sema5A in CSU and its link to IL-17A. Material and Methods: We investigated patients with CSU and healthy controls for skin expression of expressing peripheral T cells. Results: Sema5A was highly expressed in the skin of CSU patients as compared to healthy control skin. Both CD4+ T cells and mast cells in CSU skin expressed Sema5A, and many of them expressed both Sema5A and IL-17A. Patients with CSU had significantly higher rates of IL-17A-expressing CD4+ T cells as compared to healthy controls. Incubation with Sema5A increased the rates of IL-17A-expressing CD4+ T cells in healthy controls to CSU levels. Conclusion: Sema5A may drive the expression and effects of IL-17A in CSU. Further studies in larger cohorts are needed to confirm the role of Sema5A in the pathogenesis of CSU and to explore its potential as a therapeutic target. Keywords: chronic spontaneous urticaria; T cells; mast cells; semaphorin5A; IL-17 Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Fri Mar 12 08:29:01 CET 2021 ModDate: Fri Mar 12 08:35:42 CET 2021 ID: 0xdc7a02d860351afc5e2d609cd930bb38, 0xdc7a02d860351afc5e2d609cd930bb38 Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: SZMGFL+URWPalladioL-Roma FontSubset: true FirstChar: 2 LastChar: 239 FontDescriptor: FontName: SZMGFL+URWPalladioL-Roma Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: HYUQZR+TeX-tipa10 FontSubset: true FirstChar: 55 LastChar: 55 FontDescriptor: FontName: HYUQZR+TeX-tipa10 Flags: Symbolic FontBBox: -70, -296, 812, 771 FontFile: true Font: BaseFont: XKSBAY+EURM10 FontSubset: true FirstChar: 11 LastChar: 34 FontDescriptor: FontName: XKSBAY+EURM10 Flags: Symbolic FontBBox: -32, -243, 1060, 720 FontFile: true Font: BaseFont: NUNBCL+URWPalladioL-Ital FontSubset: true 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