A critical role of interleukin 17A (IL-17A) is suggested in many autoimmune and inflammatory skin disorders. Patients with bullous pemphigoid (BP), the most frequent autoimmune blistering skin disease, urgently need more specific therapy than long-term use of corticosteroids. Here, we aimed at elucidating the role of IL-17 and related cytokines in the recently developed antibody transfer-induced mouse model of BP. In this model, a significant correlation between disease activity and IL-17A serum levels was observed. To further explore the role of IL-17A, we induced experimental BP in IL-17A-deficient mice (IL-17A-/-) and mice deficient for both IL-17A and IL-17F (IL-17A/F-/-). While IL-17A-/- mice were almost completely protected from clinical disease compared to wild-type (WT) mice (p≤0.0001), at the end of the experiment, IL-17A/F-/- animals showed significantly more skin lesions compared to IL-17A-/- mice (p=0.0002) and significantly less compared to WT mice (p=0.01). In peripheral blood and skin of WT mice, significantly higher levels of IL-17A, IL-21 and IL-22 were detected compared to IL-17A-/- mice (p=0.0123, p=0.0044, p=0,0009). Interestingly, Th17 cells were found abundantly in the lesional skin of WT mice (5.95% of total cells) compared to neutrophils (3.84%). Moreover, IL-17-related genes including Il17ra, Il17rc, Tgf1, IL-23r, Il1, were down-regulated in IL-17A-/- compared to WT animals. To corroborate the findings in the IL-17A-/- mice, an inhibitory anti-IL-17A antibody was applied in a prophylactic approach. The anti-IL-17A treatment significantly reduced skin lesions compared to isotype control-injected mice (p=0.02). These data may pave the way for the future anti-IL-17A treatment in patients with BP. Next, we will apply the anti-IL-17A antibody in a quasi-therapeutic approach in mice that have developed skin lesions and aim at identifying the source and the target of IL-17A in experimental BP.

IL-17A is a key regulator in experimental bullous pemphigoid