Primary alterations during the development of hidradenitis suppurativa

Z. Dajnoki, O. Somogyi, B. Medgyesi, A. Jenei, L. Szabó, K. Gáspár, Z. Hendrik, P. Gergely, D. Imre, S. Póliska, D. Törőcsik, C. C. Zouboulis, E. P. Prens, A. Kapitány, A. Szegedi*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

18 Citations (Scopus)
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Abstract

Background: Hidradenitis suppurativa (HS) is a chronic, inflammatory disease of the apocrine gland-rich (AGR) skin region. The initial steps of disease development are not fully understood, despite intense investigations into immune alterations in lesional HS skin. Objectives: We aimed to systematically investigate the inflammatory molecules involved in three stages of HS pathogenesis, including healthy AGR, non-lesional HS and lesional HS skin, with the parallel application of multiple mRNA and protein-based methods. Methods: Immune cell counts (T cells, dendritic cells, macrophages), Th1/Th17-related molecules (IL-12B, TBX21, IFNG, TNFA, IL-17, IL10, IL-23A, TGFB1, RORC, CCL20), keratinocyte-related sensors (TLR2,4), mediators (S100A7, S100A8, S100A9, DEFB4B, LCN2, CAMP, CCL2) and pro-inflammatory molecules (IL1B, IL6, TNFA, IL-23A) were investigated in the three groups by RNASeq, RT-qPCR, immunohistochemistry and immunofluorescence. Results: Epidermal changes were already detectable in non-lesional HS skin; the epidermal occurrence of antimicrobial peptides (AMPs), IL-1β, TNF-α and IL-23 was highly upregulated compared with healthy AGR skin. In lesional HS epidermis, TNF-α and IL-1β expression remained at high levels while AMPs and IL-23 increased even more compared with non-lesional skin. In the dermis of non-lesional HS skin, signs of inflammation were barely detectable (vs. AGR), while in the lesional dermis, the number of inflammatory cells and Th1/Th17-related mediators were significantly elevated. Conclusions: Our findings that non-lesional HS epidermal keratinocytes produce not only AMPs and IL-1β but also high levels of TNF-α and IL-23 confirm the driver role of keratinocytes in HS pathogenesis and highlight the possible role of keratinocytes in the transformation of non-inflammatory Th17 cells (of healthy AGR skin) into inflammatory cells (of HS) via the production of these mediators. The fact that epidermal TNF-α and IL-23 appear also in non-lesional HS seems to prove these cytokines as excellent therapeutic targets.

Original languageEnglish
Pages (from-to)462-471
Number of pages10
JournalJournal of the European Academy of Dermatology and Venereology
Volume36
Issue number3
DOIs
Publication statusPublished - Mar 2022

Bibliographical note

Acknowledgement:
The publication is supported by Hungarian Research Grants (NKFIH K‐128250 and NKFIH PD‐131689) and EFOP‐3.6.1‐16‐2016‐00022 projects. The project is cofinanced by the European Union and the European Social Fund. This project was supported by the János Bolyai Research Scholarship of the Hungarian Academy of Sciences (AK and DZ) and is also supported by the ÚNKP‐20‐5 New National Excellence Program of the Ministry for Innovation and Technology (DZ and TD). The Department of Dermatology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary and the Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Dessau, Germany, are healthcare providers of the European Reference Network for Rare and Complex Skin Diseases (ERN Skin – ALLOCATE Skin group).

Publisher Copyright:
© 2021 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology

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