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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IL-22 Downregulates Peptidylarginine Deiminase-1 in Human Keratinocytes : Adding Another Piece to the IL-22 Puzzle in Epidermal Barrier Formation. / Padhi, Avinash; Srivastava, Ankit; Ramesh, Abarajitha; Ehrström, Marcus; Simon, Michel; Sonkoly, Enikö; Eidsmo, Liv; Bergman, Peter; Lysell, Josefin.
In: The Journal of Investigative Dermatology, Vol. 142, No. 2, 2022, p. 333-342.e6.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - IL-22 Downregulates Peptidylarginine Deiminase-1 in Human Keratinocytes
T2 - Adding Another Piece to the IL-22 Puzzle in Epidermal Barrier Formation
AU - Padhi, Avinash
AU - Srivastava, Ankit
AU - Ramesh, Abarajitha
AU - Ehrström, Marcus
AU - Simon, Michel
AU - Sonkoly, Enikö
AU - Eidsmo, Liv
AU - Bergman, Peter
AU - Lysell, Josefin
N1 - Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - Acitretin/pharmacology
KW - Biopsy
KW - Cell Differentiation/drug effects
KW - Cell Line
KW - Citrullination/drug effects
KW - Dermatitis, Atopic/drug therapy
KW - Down-Regulation
KW - Epidermis/drug effects
KW - Filaggrin Proteins/metabolism
KW - Humans
KW - Interleukins/metabolism
KW - Keratin-1/metabolism
KW - Keratinocytes/drug effects
KW - Primary Cell Culture
KW - Protein-Arginine Deiminase Type 1/genetics
KW - Psoriasis/drug therapy
KW - Vitamin D/pharmacology
U2 - 10.1016/j.jid.2021.07.155
DO - 10.1016/j.jid.2021.07.155
M3 - Journal article
C2 - 34352263
VL - 142
SP - 333-342.e6
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
SN - 0022-202X
IS - 2
ER -
ID: 312711148