PracticeUpdate Conference Series: IID 2018

Neutralization of Interleukin 17 Implicated in Inflammatory Skin Diseases Overall and in Psoriasis Specifically Interleukin 17C was explored as a checkpoint in innate skin immunology, and interleukin 17A in terms of molecular transformation. These two presentations were delivered IID 2018.

Interleukin 17C: A checkpoint in innate skin immunology F elix Lauffer, MD, of the Technische Universität München in Munich, Germany, explained that inflammatory skin diseases are frequent and exert a major impact on quality of life. While the importance of interleukin 17A is well known, other members of the interleukin 17 family, such as inter- leukin 17C, remain poorly investigated.

Cell-free supernatant of keratinocytes stimulated with interleukin 17C enhanced the migratory poten- tial of neutrophil granulocytes to a comparable level as CXCL8. To assess the relevance of interleukin 17C in a complex model of human disease, Dr. Lauffer’s team finally cultured human skin biopsies of pso- riasis and atopic dermatitis with an interleukin 17C-neutralizing antibody. Compared with untreated controls, neutralization of interleukin 17C led to significant downregulation of pro-inflammatory cytokines and antimicrobial peptides, for example, interleukin 36G (DEFB4A). This downregulation demonstrated the crucial role of interleukin 17C in human inflammatory conditions. Dr. Lauffer concluded that interleukin 17C is broadly expressed in human skin pathology, is induced by innate immune stimulative activation of NFкB, and forms a pro-inflammatory feedback loop with TNFα. Dr. Lauffer concluded, “We were able to demon- strate that interleukin 17C potentiates the inflammatory response of keratinocytes in vitro and that specific neutralization of interleukin 17C decreases inflammation in murine and human models of psoriasis and atopic dermatitis. Inhibition of interleukin 17C signaling is a promising, novel approach to treat inflammatory skin diseases.”

Dr. Lauffer told Elsevier’s PracticeUpdate , “Inflammatory skin disease are frequent and impact quality of life severely. While new therapeutic strat- egies for psoriasis have been discovered with great success, targeted therapies in other inflammatory skin diseases, such as atopic dermatitis, are still needed. We performed this study to understand how the epithelial- derived cytokine interleukin 17C can influence skin inflammation.” Dr. Lauffer and colleagues detected high numbers of interleukin 17C-positive cells in diverse inflam- matory, autoimmune, and infectious skin diseases. In keratinocytes, interleukin 17C was induced by interleukin 1β, flagellin, and tumor necrosis factor α (TNFα) via upregulation of p65, phospho-p65, and IкBα. Expression of interleukin 17C transcripts was dependent on NFкB and ERK1/2. Stimulation of interleukin 17C led to enhanced expression of antimicrobial peptides in primary human keratino- cytes. This effect was potentiated synergistically by costimulation with TNFα.

Dr. Felix Lauffer

Dr. Trine Bertelsen

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