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IL-22 Downregulates Peptidylarginine Deiminase-1 in Human Keratinocytes: Adding Another Piece to the IL-22 Puzzle in Epidermal Barrier Formation

  • Avinash Padhi
    Affiliations
    Dermatology and Venereology Section, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden

    Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Sweden
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  • Ankit Srivastava
    Affiliations
    Dermatology and Venereology Section, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden

    Department of Microbiology, Tumor and Cell Biology, Science for Life Laboratory, Karolinska Institute, Stockholm, Sweden

    The Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California, USA
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  • Abarajitha Ramesh
    Affiliations
    Department of Immunology and Microbiology, Uppsala University, Uppsala, Sweden
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  • Marcus Ehrström
    Affiliations
    Department of Reconstructive Plastic Surgery, Karolinska University Hospital Solna, Stockholm, Sweden
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  • Michel Simon
    Affiliations
    Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), University of Toulouse, Centre National de la Recherche Scientifique (CNRS), Institut national de la santé et de la recherche médicale (INSERM), UPS, Toulouse, France
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  • Enikö Sonkoly
    Affiliations
    Dermatology and Venereology Section, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden

    Center for Molecular Medicine (CMM), Karolinska Institutet, Stockholm, Sweden

    Unit of Dermatology, Karolinska University Hospital, Stockholm, Sweden
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  • Liv Eidsmo
    Affiliations
    Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden

    Diagnostiskt Centrum Hud, Stockholm, Sweden
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  • Peter Bergman
    Affiliations
    Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Sweden

    Department of Infectious Diseases, Karolinska University Hospital, Huddinge, Stockholm, Sweden
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  • Josefin Lysell
    Correspondence
    Correspondence: Josefin Lysell, Dermatology and Venereology Section, Department of Medicine Solna, Karolinska Institutet, Stockholm 171 77, Sweden.
    Affiliations
    Dermatology and Venereology Section, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden

    Unit of Dermatology, Karolinska University Hospital, Stockholm, Sweden
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Published:August 02, 2021DOI:https://doi.org/10.1016/j.jid.2021.07.155
      Increased presence of IL-22+ cells in the skin is a characteristic finding in skin barrier defects, such as psoriasis and atopic dermatitis. However, mechanistic insight into effects of IL-22 on epidermal functioning is yet to be elucidated. One crucial step during epidermal differentiation is deimination or citrullination. Here, we show reduced levels of peptidylarginine deiminase 1, an enzyme that converts peptidylarginine into citrulline in lesional psoriatic skin. IL-22 signaling through the IL-22 receptor complex was found to suppress expression of peptidylarginine deiminase 1 in epidermal keratinocytes. Subsequently, total peptidylarginine deiminase activity and extent of protein deimination in keratinocytes treated with IL-22 were reduced together with a significant decrease in deimination of keratin 1 and FLG, both important for epidermal differentiation. Vitamin D and acitretin partly restored the peptidylarginine deiminase 1 defect caused by IL-22. Collectively, we show that IL-22 downregulates deimination, thus identifying a potential target for treatment of skin barrier defects.

      Graphical abstract

      Abbreviations:

      3D (three dimensional), K (keratin), KC (keratinocyte), NHEK (normal human epidermal keratinocyte), PAD (peptidylarginine deiminase)
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      Supplementary References

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