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PLoS One. 2019 Nov 26;14(11):e0225782. doi: 10.1371/journal.pone.0225782. eCollection 2019.

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

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Department of Pathology-Immunology, University of Geneva School of Medicine, Geneva, Switzerland.
Division of Rheumatology, Department of Internal Medicine Specialties, University Hospitals, Geneva, Switzerland.
Division of Dermatology and Venereology, University Hospitals, Geneva, Switzerland.
Cell Bank, Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Cracow, Poland.
Department of Pediatric Urology, Jagiellonian University Medical College, Cracow, Poland.
Department of Plastic, Reconstructive and Aesthetic Surgery, University Hospitals of Geneva, University of Geneva School of Medicine, Geneva, Switzerland.


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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Conflict of interest statement

The authors have declared that no competing interests exist.

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