Interleukin-38 interacts with destrin/actin-depolymerizing factor in human keratinocytes.

Talabot-Ayer D; Mermoud L; Borowczyk J; Drukala J; Wolnicki M; Modarressi A; Boehncke WH; Brembilla N; Palmer G

doi:10.1371/journal.pone.0225782

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Journal article

Interleukin-38 interacts with destrin/actin-depolymerizing factor in human keratinocytes.

Talabot-Ayer D Department of Pathology-Immunology, University of Geneva School of Medicine, Geneva, Switzerland.
Mermoud L Department of Pathology-Immunology, University of Geneva School of Medicine, Geneva, Switzerland.
Borowczyk J Department of Pathology-Immunology, University of Geneva School of Medicine, Geneva, Switzerland.
Drukala J Cell Bank, Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Cracow, Poland.
Wolnicki M Department of Pediatric Urology, Jagiellonian University Medical College, Cracow, Poland.
Modarressi A Department of Plastic, Reconstructive and Aesthetic Surgery, University Hospitals of Geneva, University of Geneva School of Medicine, Geneva, Switzerland.
Boehncke WH Department of Pathology-Immunology, University of Geneva School of Medicine, Geneva, Switzerland.
Brembilla N Department of Pathology-Immunology, University of Geneva School of Medicine, Geneva, Switzerland.
Palmer G Department of Pathology-Immunology, University of Geneva School of Medicine, Geneva, Switzerland.

2019-11-27

Published in:

PloS one. - 2019

English Interleukin (IL)-38 is a member of the IL-1 family of cytokines, which was proposed to exert anti-inflammatory effects. IL-38 is constitutively expressed in the skin, where keratinocytes are the main producing cells. Little information is currently available concerning IL-38 biology. Here, we investigated the subcellular localization and interaction partners of the IL-38 protein in human keratinocytes. IL-38 expression was reduced in primary keratinocytes grown in monolayer (2D) cultures. We thus used IL-38 overexpressing immortalized normal human keratinocytes (NHK/38) to study this cytokine in cell monolayers. In parallel, differentiation of primary human keratinocytes in an in vitro reconstructed human epidermis (RHE) 3D model allowed us to restore endogenous IL-38 expression. In NHK/38 cells and in RHE, IL-38 was mainly cell-associated, rather than released into culture supernatants. Intracellular IL-38 was preferentially, although not exclusively, cytoplasmic. Similarly, in normal human skin sections, IL-38 was predominantly cytoplasmic in the epidermis and essentially excluded from keratinocyte nuclei. A yeast two-hybrid screen identified destrin/actin-depolymerizing factor (DSTN) as a potential IL-38-interacting molecule. Co-immunoprecipitation and proximity ligation assay confirmed this interaction. We further observed partial co-localization of IL-38 and DSTN in NHK/38 cells. Endogenous IL-38 and DSTN were also co-expressed in all epidermal layers in RHE and in normal human skin. Finally, IL-38 partially co-localized with F-actin in NHK/38 cells, in particular along the cortical actin network and in filopodia. In conclusion, IL-38 is found predominantly in the cytoplasm of human keratinocytes, where it interacts with DSTN. The functional relevance of this interaction remains to be investigated.

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