IL-37 Expression Is Downregulated in Lesional Psoriasis Skin

Kirsten Rønholt; Ane Langkilde-Lauesen Nielsen; Claus Johansen; Christian Vestergaard; Astrid Fauerbye; Rubèn López-Vales; Charles A Dinarello; Lars Iversen

doi:10.4049/immunohorizons.2000083

IL-37 Expression Is Downregulated in Lesional Psoriasis Skin

Kirsten Rønholt, Ane Langkilde-Lauesen Nielsen, Claus Johansen, Christian Vestergaard, Astrid Fauerbye, Rubèn López-Vales, Charles A Dinarello, Lars Iversen

Institut for Klinisk Medicin - Hud- og Kønssygdomme

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

Abstract

IL-37 broadly suppresses inflammation in various disease models. However, studies of the regulation and role of IL-37 in psoriasis are limited and contradictive. Using transcriptome analysis, PCR, protein determination, and immunofluorescence, we demonstrated marked downregulation of IL-37 in biopsies from human lesional psoriasis skin compared with paired samples of nonlesional skin. Immunofluorescence analysis showed that IL-37 was localized to stratum granulosum of the epidermis. TNF-a stimulation of normal human epidermal keratinocytes led to increased IL37 expression through a p38 MAPK-mediated mechanism, whereas IL-17A, IL-17C, IL-17F, and IL-22 acted suppressively. Intradermal injection with recombinant human IL-37 into imiquimod-induced psoriasis skin of C57BL/6J mice demonstrated a trend toward a protective effect, however NS. Altogether, these results demonstrate that IL-37 is downregulated in human lesional psoriasis skin. This may be a consequence of the loss of stratum granulosum, but key cytokines in the development of psoriasis also seem to contribute to this downregulation.

Originalsprog	Engelsk
Tidsskrift	ImmunoHorizons
Vol/bind	4
Nummer	11
Sider (fra-til)	754-761
Antal sider	8
ISSN	2573-7732
DOI	https://doi.org/10.4049/immunohorizons.2000083
Status	Udgivet - nov. 2020

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10.4049/immunohorizons.2000083Licens: CC BY

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title = "IL-37 Expression Is Downregulated in Lesional Psoriasis Skin",

abstract = "IL-37 broadly suppresses inflammation in various disease models. However, studies of the regulation and role of IL-37 in psoriasis are limited and contradictive. Using transcriptome analysis, PCR, protein determination, and immunofluorescence, we demonstrated marked downregulation of IL-37 in biopsies from human lesional psoriasis skin compared with paired samples of nonlesional skin. Immunofluorescence analysis showed that IL-37 was localized to stratum granulosum of the epidermis. TNF-a stimulation of normal human epidermal keratinocytes led to increased IL37 expression through a p38 MAPK-mediated mechanism, whereas IL-17A, IL-17C, IL-17F, and IL-22 acted suppressively. Intradermal injection with recombinant human IL-37 into imiquimod-induced psoriasis skin of C57BL/6J mice demonstrated a trend toward a protective effect, however NS. Altogether, these results demonstrate that IL-37 is downregulated in human lesional psoriasis skin. This may be a consequence of the loss of stratum granulosum, but key cytokines in the development of psoriasis also seem to contribute to this downregulation.",

author = "Kirsten R{\o}nholt and Nielsen, {Ane Langkilde-Lauesen} and Claus Johansen and Christian Vestergaard and Astrid Fauerbye and Rub{\`e}n L{\'o}pez-Vales and Dinarello, {Charles A} and Lars Iversen",

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year = "2020",

month = nov,

doi = "10.4049/immunohorizons.2000083",

language = "English",

volume = "4",

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T1 - IL-37 Expression Is Downregulated in Lesional Psoriasis Skin

AU - Rønholt, Kirsten

AU - Nielsen, Ane Langkilde-Lauesen

AU - Johansen, Claus

AU - Vestergaard, Christian

AU - Fauerbye, Astrid

AU - López-Vales, Rubèn

AU - Dinarello, Charles A

AU - Iversen, Lars

PY - 2020/11

Y1 - 2020/11

N2 - IL-37 broadly suppresses inflammation in various disease models. However, studies of the regulation and role of IL-37 in psoriasis are limited and contradictive. Using transcriptome analysis, PCR, protein determination, and immunofluorescence, we demonstrated marked downregulation of IL-37 in biopsies from human lesional psoriasis skin compared with paired samples of nonlesional skin. Immunofluorescence analysis showed that IL-37 was localized to stratum granulosum of the epidermis. TNF-a stimulation of normal human epidermal keratinocytes led to increased IL37 expression through a p38 MAPK-mediated mechanism, whereas IL-17A, IL-17C, IL-17F, and IL-22 acted suppressively. Intradermal injection with recombinant human IL-37 into imiquimod-induced psoriasis skin of C57BL/6J mice demonstrated a trend toward a protective effect, however NS. Altogether, these results demonstrate that IL-37 is downregulated in human lesional psoriasis skin. This may be a consequence of the loss of stratum granulosum, but key cytokines in the development of psoriasis also seem to contribute to this downregulation.

AB - IL-37 broadly suppresses inflammation in various disease models. However, studies of the regulation and role of IL-37 in psoriasis are limited and contradictive. Using transcriptome analysis, PCR, protein determination, and immunofluorescence, we demonstrated marked downregulation of IL-37 in biopsies from human lesional psoriasis skin compared with paired samples of nonlesional skin. Immunofluorescence analysis showed that IL-37 was localized to stratum granulosum of the epidermis. TNF-a stimulation of normal human epidermal keratinocytes led to increased IL37 expression through a p38 MAPK-mediated mechanism, whereas IL-17A, IL-17C, IL-17F, and IL-22 acted suppressively. Intradermal injection with recombinant human IL-37 into imiquimod-induced psoriasis skin of C57BL/6J mice demonstrated a trend toward a protective effect, however NS. Altogether, these results demonstrate that IL-37 is downregulated in human lesional psoriasis skin. This may be a consequence of the loss of stratum granulosum, but key cytokines in the development of psoriasis also seem to contribute to this downregulation.

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U2 - 10.4049/immunohorizons.2000083

DO - 10.4049/immunohorizons.2000083

M3 - Journal article

C2 - 33239358

SN - 2573-7732

VL - 4

SP - 754

EP - 761

JO - ImmunoHorizons

JF - ImmunoHorizons

IS - 11

ER -

IL-37 Expression Is Downregulated in Lesional Psoriasis Skin

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