Interleukin-17C (IL-17C) increases epithelial inflammation in skin and amplifies keratinocyte-derived pro-inflammatory signals in animal and human models of psoriasis and atopic eczema, suggesting IL-17C may be a treatment target for inflammatory skin diseases, study data in the Journal of the European Academy of Dermatology and Venereology reports.

The study employed human skin samples and blood cells. Researchers stimulated primary human keratinocytes and used qRT-PCR and Luminex® assay to determine the expression of cytokines and chemokines. In addition, the investigators examined neutrophil migration towards supernatant of the stimulated keratinocytes. Immunochemistry and transcriptome analysis were used to assess IL-17C gene and protein expression. Researchers also employed MOR106, a new IL-17C specific antibody, to deplete IL-17C in murine models of psoriasis and atopic eczema. Depletion of IL-17C was also performed in human skin biopsies of psoriasis and atopic eczema.

Compared with non-lesional skin there was noticeable and enhanced expression of IL-17C mRNA in all inflammatory skin conditions. Both IL-17C and TNA-α, taken together, enhanced expression of IL-36G, S100A7, and HBD2, all of which are proteins enhanced in inflammatory skin lesions.

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In addition, the study found that IL-17C potentiates the expression of several chemokines, including CXCL8, CXCL10, CCL5, and VEGF. Depletion of IL-17C led to significant reductions in the number of T cells, neutrophils, and eosinophils in animal models of psoriasis and atopic eczema. This depletion of IL-17C resulted in downregulation of inflammatory mediators found in the human skin biopsy models of psoriasis and atopic eczema ex vivo.

A study limitation was the use of murine models of psoriasis and atopic dermatitis, which may limit generalizability of the findings with regard to human models.

“Given the significant decrease of immune cell influx in murine models and the downregulation of target genes in human skin biopsies of psoriasis and AE after IL-17C depletion,” the researchers wrote, “IL-17C is a promising drug target for the treatment of inflammatory skin disease.”

Disclosure: This clinical trial was supported by Galapagos NV and Morphosys AG. Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

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Reference

Lauffer F, Jargosch M, Baghin V, et al. IL-17C amplifies epithelial inflammation in human psoriasis and atopic eczema [published online December 2, 2019]. J Eur Acad Dermatol Venereol. doi:10.1111/jdv.16126