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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
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- Padhi, Avinash (author)
- Karolinska Institutet,Karolinska Inst, Dept Med Solna, Dermatol & Venereol Sect, S-17177 Stockholm, Sweden.;Karolinska Inst, Dept Lab Med, Div Clin Microbiol, Stockholm, Sweden.
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- Srivastava, Ankit (author)
- Karolinska Institutet,Karolinska Inst, Dept Med Solna, Dermatol & Venereol Sect, S-17177 Stockholm, Sweden.;Karolinska Inst, Sci Life Lab, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden.;Stanford Univ, Sch Med, Program Epithelial Biol, Stanford, CA 94305 USA.
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- Ramesh, Abarajitha (author)
- Karolinska Institutet,Uppsala universitet,Mikrobiologi och immunologi
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- Karolinska Institutet Karolinska Inst, Dept Med Solna, Dermatol & Venereol Sect, S-17177 Stockholm, Sweden;Karolinska Inst, Dept Lab Med, Div Clin Microbiol, Stockholm, Sweden. (creator_code:org_t)
- Elsevier, 2022
- 2022
- English.
- In: Journal of Investigative Dermatology. - : Elsevier. - 0022-202X .- 1523-1747. ; 142:2, s. 333-342.e6
- Journal article (peer-reviewed)
Abstract
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Dermatologi och venereologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Dermatology and Venereal Diseases (hsv//eng)
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