139 Local dermatitis upon tapestripping and vaseline treatment of healthy human skin is attenuated by coal tar: insights into AHR-targeting therapies for inflammatory skin diseases

Abstract

Coal tar therapy, an old dermatological therapy, exerts its therapeutic effect through activation of the aryl hydrocarbon receptor (AHR) and AHR-targeting molecules show therapeutic efficacy in phase 2/3 trials for chronic inflammatory skin diseases. The anti-inflammatory mechanisms of AHR activation in the skin are partially understood, but mostly studied in animal models. Here we aimed to investigate the therapeutic effects of AHR activation by coal tar application on epidermal responses after skin barrier disruption and inflammatory cues in human skin. Healthy volunteers (n=9) were treated with pix lithanthracis (5% in vaseline lanette) or vehicle (vaseline lanette) after complete removal of the stratum corneum by tape stripping. Non-invasive biophysical measurements (TEWL, hydration, erythema), stratum corneum tapes (NMF and protein profiling) and biopies were taken during 4 days of treatment. Application of vaseline on tapestripped skin led to an acute inflammatory response characterized by increased keratinocyte proliferation and subsequent acanthosis, a dense dermal CD45+ and MPO+ immune cell infiltrate indicative of (neutrophilic) granulocytes and increased levels of human beta defensin-2 (hBD2). Most strikingly, coal tar treated sites clearly showed less immune cell infiltrate, less pronounced acanthosis and hBD2 levels in the stratum corneum were significantly lower than upon vaseline treatment. No differential effects were found between vaseline and coal tar treatment for the other parameters we investigated. This in vivo human acute dermatitis model indicates that activation of AHR signaling reduces the influx of inflammatory cells potentially resulting in less epidermal activation. The lack in positive effects on skin barrier parameters by coal tar may be due to the relative short study period. Further investigations on the inflammatory signaling molecules driving the acute inflammation can provide new insights in the coal tar and AHR-mediated therapeutic effects.