{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T02:15:53Z","timestamp":1787796953750,"version":"build-2784847793"},"reference-count":121,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T00:00:00Z","timestamp":1693353600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Psoriasis Association"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>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\u2013nerve fibre interaction. Furthermore, the analysis of 208 identified itch-associated genes revealed that CTSB, TLR4, and TACR1 were upregulated in MCs in involved skin. In both whole-skin published datasets and isolated MCs, CTSB 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.<\/jats:p>","DOI":"10.3390\/cells12172177","type":"journal-article","created":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T09:48:15Z","timestamp":1693388895000},"page":"2177","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Human Mast Cells Upregulate Cathepsin B, a Novel Marker of Itch in Psoriasis"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0097-5006","authenticated-orcid":false,"given":"Peter W.","family":"West","sequence":"first","affiliation":[{"name":"Lydia 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, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Tontini","sequence":"additional","affiliation":[{"name":"Lydia 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, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haris","family":"Atmoko","sequence":"additional","affiliation":[{"name":"Lydia 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, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orsolya","family":"Kiss","sequence":"additional","affiliation":[{"name":"Lydia 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, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terence","family":"Garner","sequence":"additional","affiliation":[{"name":"Division 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, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajia","family":"Bahri","sequence":"additional","affiliation":[{"name":"Lydia 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, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard B.","family":"Warren","sequence":"additional","affiliation":[{"name":"Lydia 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, UK"},{"name":"Centre for Dermatology Research, The University of Manchester & Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester M23 9LT, UK"},{"name":"NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester M23 9LT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5371-4427","authenticated-orcid":false,"given":"Christopher E. M.","family":"Griffiths","sequence":"additional","affiliation":[{"name":"Lydia 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, UK"},{"name":"Centre for Dermatology Research, The University of Manchester & Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester M23 9LT, UK"},{"name":"NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester M23 9LT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1950-7325","authenticated-orcid":false,"given":"Adam","family":"Stevens","sequence":"additional","affiliation":[{"name":"Division 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, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5764-8516","authenticated-orcid":false,"given":"Silvia","family":"Bulfone-Paus","sequence":"additional","affiliation":[{"name":"Lydia 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, UK"},{"name":"Centre for Dermatology Research, The University of Manchester & Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester M23 9LT, UK"},{"name":"NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester M23 9LT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2433","DOI":"10.1016\/j.jid.2020.03.963","article-title":"Mast Cells Occupy Stable Clonal Territories in Adult Steady-State Skin","volume":"120","author":"Weitzmann","year":"2020","journal-title":"J. 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