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-α 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.

• Authors: Kirsten Rønholt, Ane Langkilde-Lauesen Nielsen, Claus Johansen, Christian Vestergaard, Astrid Fauerbye, Rubèn López-Vales, Charles A Dinarello, Lars Iversen
• Journal: ImmunoHorizons (Immunohorizons) Vol. 4 Issue 11 Pg. 754-761 (11 25 2020) ISSN: 2573-7732 [Electronic] United States
• PMID: 33239358 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 The Authors.

Chemical References

• IL37 protein, human
• Interleukin-1
• Interleukin-17
• Tumor Necrosis Factor-alpha
• Imiquimod

Topics

• Animals
• Cells, Cultured
• Disease Models, Animal
• Down-Regulation
• Female
• Humans
• Imiquimod
• Inflammation (metabolism)
• Interleukin-1 (genetics, metabolism)
• Interleukin-17 (metabolism)
• Keratinocytes (pathology)
• Mice
• Mice, Inbred C57BL
• Psoriasis (metabolism, pathology)
• Tumor Necrosis Factor-alpha (metabolism)