Transcriptional Analysis-Based Alterations Affecting Neuritogenesis of the Peripheral Nervous System in Psoriasis
An increasing amount of evidence indicates the critical role of the cutaneous nervous system in the initiation and maintenance of psoriatic skin lesions by neurogenic inflammation. However, molecular mechanisms affecting cutaneous neurons are largely uncharacterized. Therefore, we reanalyzed a psori...
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MDPI AG
2022-01-01
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| Series: | Life |
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| Online Access: | https://www.mdpi.com/2075-1729/12/1/111 |
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| author | Dóra Romhányi Kornélia Szabó Lajos Kemény Endre Sebestyén Gergely Groma |
| author_facet | Dóra Romhányi Kornélia Szabó Lajos Kemény Endre Sebestyén Gergely Groma |
| author_sort | Dóra Romhányi |
| collection | DOAJ |
| description | An increasing amount of evidence indicates the critical role of the cutaneous nervous system in the initiation and maintenance of psoriatic skin lesions by neurogenic inflammation. However, molecular mechanisms affecting cutaneous neurons are largely uncharacterized. Therefore, we reanalyzed a psoriatic RNA sequencing dataset from published transcriptome experiments of nearly 300 individuals. Using the Ingenuity Pathway Analysis software, we associated several hundreds of differentially expressed transcripts (DETs) to nervous system development and functions. Since neuronal projections were previously reported to be affected in psoriasis, we performed an in-depth analysis of neurite formation-related process. Our <i>in silico</i> analysis suggests that SEMA-PLXN and ROBO-DCC-UNC5 regulating axonal growth and repulsion are differentially affected in non-lesional and lesional skin samples. We identified opposing expressional alterations in secreted ligands for axonal guidance signaling (RTN4/NOGOA, NTNs, SEMAs, SLITs) and non-conventional axon guidance regulating ligands, including WNT5A and their receptors, modulating axon formation. These differences in neuritogenesis may explain the abnormal cutaneous nerve filament formation described in psoriatic skin. The processes also influence T-cell activation and infiltration, thus highlighting an additional angle of the crosstalk between the cutaneous nervous system and the immune responses in psoriasis pathogenesis, in addition to the known neurogenic pro-inflammatory mediators. |
| first_indexed | 2024-03-10T01:06:24Z |
| format | Article |
| id | doaj.art-5e4c1bf64ce046c197b05a00d5929b4a |
| institution | Directory Open Access Journal |
| issn | 2075-1729 |
| language | English |
| last_indexed | 2024-03-10T01:06:24Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Life |
| spelling | doaj.art-5e4c1bf64ce046c197b05a00d5929b4a2023-11-23T14:25:13ZengMDPI AGLife2075-17292022-01-0112111110.3390/life12010111Transcriptional Analysis-Based Alterations Affecting Neuritogenesis of the Peripheral Nervous System in PsoriasisDóra Romhányi0Kornélia Szabó1Lajos Kemény2Endre Sebestyén3Gergely Groma4Department of Dermatology and Allergology, University of Szeged, H-6720 Szeged, HungaryDepartment of Dermatology and Allergology, University of Szeged, H-6720 Szeged, HungaryDepartment of Dermatology and Allergology, University of Szeged, H-6720 Szeged, Hungary1st Department of Pathology and Experimental Cancer Research, Semmelweis University, H-1085 Budapest, HungaryDepartment of Dermatology and Allergology, University of Szeged, H-6720 Szeged, HungaryAn increasing amount of evidence indicates the critical role of the cutaneous nervous system in the initiation and maintenance of psoriatic skin lesions by neurogenic inflammation. However, molecular mechanisms affecting cutaneous neurons are largely uncharacterized. Therefore, we reanalyzed a psoriatic RNA sequencing dataset from published transcriptome experiments of nearly 300 individuals. Using the Ingenuity Pathway Analysis software, we associated several hundreds of differentially expressed transcripts (DETs) to nervous system development and functions. Since neuronal projections were previously reported to be affected in psoriasis, we performed an in-depth analysis of neurite formation-related process. Our <i>in silico</i> analysis suggests that SEMA-PLXN and ROBO-DCC-UNC5 regulating axonal growth and repulsion are differentially affected in non-lesional and lesional skin samples. We identified opposing expressional alterations in secreted ligands for axonal guidance signaling (RTN4/NOGOA, NTNs, SEMAs, SLITs) and non-conventional axon guidance regulating ligands, including WNT5A and their receptors, modulating axon formation. These differences in neuritogenesis may explain the abnormal cutaneous nerve filament formation described in psoriatic skin. The processes also influence T-cell activation and infiltration, thus highlighting an additional angle of the crosstalk between the cutaneous nervous system and the immune responses in psoriasis pathogenesis, in addition to the known neurogenic pro-inflammatory mediators.https://www.mdpi.com/2075-1729/12/1/111psoriasiscutaneous nervous systemaxon developmentmyelination |
| spellingShingle | Dóra Romhányi Kornélia Szabó Lajos Kemény Endre Sebestyén Gergely Groma Transcriptional Analysis-Based Alterations Affecting Neuritogenesis of the Peripheral Nervous System in Psoriasis Life psoriasis cutaneous nervous system axon development myelination |
| title | Transcriptional Analysis-Based Alterations Affecting Neuritogenesis of the Peripheral Nervous System in Psoriasis |
| title_full | Transcriptional Analysis-Based Alterations Affecting Neuritogenesis of the Peripheral Nervous System in Psoriasis |
| title_fullStr | Transcriptional Analysis-Based Alterations Affecting Neuritogenesis of the Peripheral Nervous System in Psoriasis |
| title_full_unstemmed | Transcriptional Analysis-Based Alterations Affecting Neuritogenesis of the Peripheral Nervous System in Psoriasis |
| title_short | Transcriptional Analysis-Based Alterations Affecting Neuritogenesis of the Peripheral Nervous System in Psoriasis |
| title_sort | transcriptional analysis based alterations affecting neuritogenesis of the peripheral nervous system in psoriasis |
| topic | psoriasis cutaneous nervous system axon development myelination |
| url | https://www.mdpi.com/2075-1729/12/1/111 |
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