Psoriatic Resolved Skin Epidermal Keratinocytes Retain Disease-Residual Transcriptomic and Epigenomic Profiles

Author:

Ghaffarinia Ameneh12,Ayaydin Ferhan345,Póliska Szilárd6ORCID,Manczinger Máté278,Bolla Beáta Szilvia12,Flink Lili Borbála12ORCID,Balogh Fanni129,Veréb Zoltán1011,Bozó Renáta129ORCID,Szabó Kornélia129,Bata-Csörgő Zsuzsanna129,Kemény Lajos129ORCID

Affiliation:

1. HCEMM-USZ Skin Research Group, H-6720 Szeged, Hungary

2. Department of Dermatology and Allergology, Albert Szent-Györgyi Medical School, University of Szeged, H-6720 Szeged, Hungary

3. HCEMM-USZ, Functional Cell Biology and Immunology, Advanced Core Facility, H-6728 Szeged, Hungary

4. Laboratory of Cellular Imaging, Biological Research Centre, Eötvös Loránd Research Network, H-6726 Szeged, Hungary

5. Institute of Plant Biology, Biological Research Centre, H-6726 Szeged, Hungary

6. Genomic Medicine and Bioinformatics Core Facility, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary

7. Systems Immunology Research Group, Institute of Biochemistry, Biological Research Centre, ELKH, H-6726 Szeged, Hungary

8. HCEMM-Systems Immunology Research Group, H-6726 Szeged, Hungary

9. ELKH-SZTE Dermatological Research Group, Department of Dermatology and Allergology, University of Szeged, H-6720 Szeged, Hungary

10. Regenerative Medicine and Cellular Pharmacology Laboratory (HECRIN), Department of Dermatology and Allergology, University of Szeged, H-6720 Szeged, Hungary

11. Research Institute of Translational Biomedicine, Department of Dermatology and Allergology, University of Szeged, H-6720 Szeged, Hungary

Abstract

The disease-residual transcriptomic profile (DRTP) within psoriatic healed/resolved skin and epidermal tissue-resident memory T (TRM) cells have been proposed to be crucial for the recurrence of old lesions. However, it is unclear whether epidermal keratinocytes are involved in disease recurrence. There is increasing evidence regarding the importance of epigenetic mechanisms in the pathogenesis of psoriasis. Nonetheless, the epigenetic changes that contribute to the recurrence of psoriasis remain unknown. The aim of this study was to elucidate the role of keratinocytes in psoriasis relapse. The epigenetic marks 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) were visualized using immunofluorescence staining, and RNA sequencing was performed on paired never-lesional and resolved epidermal and dermal compartments of skin from psoriasis patients. We observed diminished 5-mC and 5-hmC amounts and decreased mRNA expression of the ten-eleven translocation (TET) 3 enzyme in the resolved epidermis. SAMHD1, C10orf99, and AKR1B10: the highly dysregulated genes in resolved epidermis are known to be associated with pathogenesis of psoriasis, and the DRTP was enriched in WNT, TNF, and mTOR signaling pathways. Our results suggest that epigenetic changes detected in epidermal keratinocytes of resolved skin may be responsible for the DRTP in the same regions. Thus, the DRTP of keratinocytes may contribute to site-specific local relapse.

Funder

EU’s Horizon 2020 research and innovation program

Hungarian scientific research funds

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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