Cutaneous lesions in psoriatic arthritis are enriched in chemokine transcriptomic pathways

Johnsson, H., Cole, J., Siebert, S. , McInnes, I. B. and Graham, G. (2023) Cutaneous lesions in psoriatic arthritis are enriched in chemokine transcriptomic pathways. Arthritis Research and Therapy, 25, 73. (doi: 10.1186/s13075-023-03034-6) (PMID:37131254) (PMCID:PMC10152590)

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Objectives: Skin from people with psoriasis has been extensively studied and is assumed to be identical to skin from those with psoriatic arthritis (PsA). Chemokines and the CC chemokine scavenger receptor ACKR2 are upregulated in uninvolved psoriasis. ACKR2 has been proposed as a regulator of cutaneous inflammation in psoriasis. The aim of this study was to compare the transcriptome of PsA skin to healthy control (HC) skin and evaluate ACKR2 expression in PsA skin. Methods: Full-thickness skin biopsies from HC, lesional and uninvolved skin from participants with PsA were sequenced on NovaSeq 6000. Findings were validated using qPCR and RNAscope. Results: Nine HC and nine paired PsA skin samples were sequenced. PsA uninvolved skin was transcriptionally similar to HC skin, and lesional PsA skin was enriched in epidermal and inflammatory genes. Lesional PsA skin was enriched in chemokine-mediated signalling pathways, but uninvolved skin was not. ACKR2 was upregulated in lesional PsA skin but had unchanged expression in uninvolved compared with HC skin. The expression of ACKR2 was confirmed by qPCR, and RNAscope demonstrated strong expression of ACKR2 in the suprabasal layer of the epidermis in PsA lesions. Conclusion: Chemokines and their receptors are upregulated in lesional PsA skin but relatively unchanged in uninvolved PsA skin. In contrast to previous psoriasis studies, ACKR2 was not upregulated in uninvolved PsA skin. Further understanding of the chemokine system in PsA may help to explain why inflammation spreads from the skin to the joints in some people with psoriasis.

Item Type:Articles
Glasgow Author(s) Enlighten ID:McInnes, Professor Iain and Siebert, Professor Stefan and Cole, Mr John and Johnsson, Dr Hanna and Graham, Professor Gerard
Authors: Johnsson, H., Cole, J., Siebert, S., McInnes, I. B., and Graham, G.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Research Centre:College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Immunobiology
Journal Name:Arthritis Research and Therapy
Publisher:BioMed Central
ISSN (Online):1478-6362
Copyright Holders:Copyright © 2023 The Authors
First Published:First published in Arthritis Research and Therapy 25: 73
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
173867ACKR2 in inflammatory arthritisHanna JohnssonOffice of the Chief Scientific Adviser (CSO)CAF/16/06Institute of Infection, Immunity & Inflammation
171627The ACKR2-CCR2 axis in development and diseaseGerard GrahamMedical Research Council (MRC)MR/M019764/1III - Immunology
306649Defining chemokine receptor involvement in the myelomonocytic inflammatory responseGerard GrahamWellcome Trust (WELLCOTR)217093/Z/19/ZIII - Immunology