Human Mast Cells Upregulate Cathepsin B, a Novel Marker of Itch in Psoriasis
Mast cells (MCs) contribute to skin inflammation. In psoriasis, the activation of cutaneous neuroimmune networks commonly leads to itch. To dissect the unique contribution of MCs to the cutaneous neuroinflammatory response in psoriasis, we examined their density, distribution, relation to nerve fibr...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-08-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/12/17/2177 |
| _version_ | 1797582718544904192 |
|---|---|
| author | Peter W. West Chiara Tontini Haris Atmoko Orsolya Kiss Terence Garner Rajia Bahri Richard B. Warren Christopher E. M. Griffiths Adam Stevens Silvia Bulfone-Paus |
| author_facet | Peter W. West Chiara Tontini Haris Atmoko Orsolya Kiss Terence Garner Rajia Bahri Richard B. Warren Christopher E. M. Griffiths Adam Stevens Silvia Bulfone-Paus |
| author_sort | Peter W. West |
| collection | DOAJ |
| description | Mast cells (MCs) contribute to skin inflammation. In psoriasis, the activation of cutaneous neuroimmune networks commonly leads to itch. To dissect the unique contribution of MCs to the cutaneous neuroinflammatory response in psoriasis, we examined their density, distribution, relation to nerve fibres and disease severity, and molecular signature by comparing RNA-seq analysis of MCs isolated from the skin of psoriasis patients and healthy volunteers. In involved psoriasis skin, MCs and Calcitonin Gene-Related Peptide (CGRP)-positive nerve fibres were spatially associated, and the increase of both MC and nerve fibre density correlated with disease severity. Gene set enrichment analysis of differentially expressed genes in involved psoriasis skin showed significant representation of neuron-related pathways (i.e., regulation of neuron projection along with dendrite and dendritic spine morphogenesis), indicating MC engagement in neuronal development and supporting the evidence of close MC–nerve fibre interaction. Furthermore, the analysis of 208 identified itch-associated genes revealed that <i>CTSB</i>, <i>TLR4</i>, and <i>TACR1</i> were upregulated in MCs in involved skin. In both whole-skin published datasets and isolated MCs, <i>CTSB</i> was found to be a reliable indicator of the psoriasis condition. Furthermore, cathepsin B+ cells were increased in psoriasis skin and cathepsin B+ MC density correlated with disease severity. Therefore, our study provides evidence that cathepsin B could serve as a common indicator of the MC-dependent itch signature in psoriasis. |
| first_indexed | 2024-03-10T23:25:23Z |
| format | Article |
| id | doaj.art-238c43347a2a4ea4bd312259b902c496 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T23:25:23Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-238c43347a2a4ea4bd312259b902c4962023-11-19T07:58:19ZengMDPI AGCells2073-44092023-08-011217217710.3390/cells12172177Human Mast Cells Upregulate Cathepsin B, a Novel Marker of Itch in PsoriasisPeter W. West0Chiara Tontini1Haris Atmoko2Orsolya Kiss3Terence Garner4Rajia Bahri5Richard B. Warren6Christopher E. M. Griffiths7Adam Stevens8Silvia Bulfone-Paus9Lydia Becker Institute of Immunology and Inflammation, Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9PT, UKLydia Becker Institute of Immunology and Inflammation, Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9PT, UKLydia Becker Institute of Immunology and Inflammation, Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9PT, UKLydia Becker Institute of Immunology and Inflammation, Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9PT, UKDivision of Developmental Biology and Medicine, Manchester Institute for Collaborative Research on Ageing, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester M23 9LT, UKLydia Becker Institute of Immunology and Inflammation, Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9PT, UKLydia Becker Institute of Immunology and Inflammation, Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9PT, UKLydia Becker Institute of Immunology and Inflammation, Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9PT, UKDivision of Developmental Biology and Medicine, Manchester Institute for Collaborative Research on Ageing, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester M23 9LT, UKLydia Becker Institute of Immunology and Inflammation, Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9PT, UKMast cells (MCs) contribute to skin inflammation. In psoriasis, the activation of cutaneous neuroimmune networks commonly leads to itch. To dissect the unique contribution of MCs to the cutaneous neuroinflammatory response in psoriasis, we examined their density, distribution, relation to nerve fibres and disease severity, and molecular signature by comparing RNA-seq analysis of MCs isolated from the skin of psoriasis patients and healthy volunteers. In involved psoriasis skin, MCs and Calcitonin Gene-Related Peptide (CGRP)-positive nerve fibres were spatially associated, and the increase of both MC and nerve fibre density correlated with disease severity. Gene set enrichment analysis of differentially expressed genes in involved psoriasis skin showed significant representation of neuron-related pathways (i.e., regulation of neuron projection along with dendrite and dendritic spine morphogenesis), indicating MC engagement in neuronal development and supporting the evidence of close MC–nerve fibre interaction. Furthermore, the analysis of 208 identified itch-associated genes revealed that <i>CTSB</i>, <i>TLR4</i>, and <i>TACR1</i> were upregulated in MCs in involved skin. In both whole-skin published datasets and isolated MCs, <i>CTSB</i> was found to be a reliable indicator of the psoriasis condition. Furthermore, cathepsin B+ cells were increased in psoriasis skin and cathepsin B+ MC density correlated with disease severity. Therefore, our study provides evidence that cathepsin B could serve as a common indicator of the MC-dependent itch signature in psoriasis.https://www.mdpi.com/2073-4409/12/17/2177mast cellscathepsin Bpsoriasisitch |
| spellingShingle | Peter W. West Chiara Tontini Haris Atmoko Orsolya Kiss Terence Garner Rajia Bahri Richard B. Warren Christopher E. M. Griffiths Adam Stevens Silvia Bulfone-Paus Human Mast Cells Upregulate Cathepsin B, a Novel Marker of Itch in Psoriasis Cells mast cells cathepsin B psoriasis itch |
| title | Human Mast Cells Upregulate Cathepsin B, a Novel Marker of Itch in Psoriasis |
| title_full | Human Mast Cells Upregulate Cathepsin B, a Novel Marker of Itch in Psoriasis |
| title_fullStr | Human Mast Cells Upregulate Cathepsin B, a Novel Marker of Itch in Psoriasis |
| title_full_unstemmed | Human Mast Cells Upregulate Cathepsin B, a Novel Marker of Itch in Psoriasis |
| title_short | Human Mast Cells Upregulate Cathepsin B, a Novel Marker of Itch in Psoriasis |
| title_sort | human mast cells upregulate cathepsin b a novel marker of itch in psoriasis |
| topic | mast cells cathepsin B psoriasis itch |
| url | https://www.mdpi.com/2073-4409/12/17/2177 |
| work_keys_str_mv | AT peterwwest humanmastcellsupregulatecathepsinbanovelmarkerofitchinpsoriasis AT chiaratontini humanmastcellsupregulatecathepsinbanovelmarkerofitchinpsoriasis AT harisatmoko humanmastcellsupregulatecathepsinbanovelmarkerofitchinpsoriasis AT orsolyakiss humanmastcellsupregulatecathepsinbanovelmarkerofitchinpsoriasis AT terencegarner humanmastcellsupregulatecathepsinbanovelmarkerofitchinpsoriasis AT rajiabahri humanmastcellsupregulatecathepsinbanovelmarkerofitchinpsoriasis AT richardbwarren humanmastcellsupregulatecathepsinbanovelmarkerofitchinpsoriasis AT christopheremgriffiths humanmastcellsupregulatecathepsinbanovelmarkerofitchinpsoriasis AT adamstevens humanmastcellsupregulatecathepsinbanovelmarkerofitchinpsoriasis AT silviabulfonepaus humanmastcellsupregulatecathepsinbanovelmarkerofitchinpsoriasis |