IL-17A is functionally relevant and a potential therapeutic target in bullous pemphigoid

Lenche Chakievska, Maike M. Holtsche, Axel Künstner, Stephanie Goletz, Britt Sabina Petersen, Diamant Thaci, Saleh M. Ibrahim, Ralf J. Ludwig, Andre Franke, Christian D. Sadik, Detlef Zillikens, Christoph Hölscher, Hauke Busch, Enno Schmidt*

*Corresponding author for this work


IL-17A has been identified as key regulatory molecule in several autoimmune and chronic inflammatory diseases followed by the successful use of anti-IL-17 therapy, e.g. in ankylosing spondylitis and psoriasis. Bullous pemphigoid (BP) is the most frequent autoimmune blistering disease with a high need for more specific, effective and safe treatment options. The aim of this study was to clarify the pathophysiological importance of IL-17A in BP. We found elevated numbers of IL-17A+ CD4+ lymphocytes in the peripheral blood of BP patients and identified CD3+ cells as major source of IL-17A in early BP skin lesions. IL17A and related genes were upregulated in BP skin and exome sequencing of 51 BP patients revealed mutations in twelve IL-17-related genes in 18 patients. We have subsequently found several lines of evidence suggesting a significant role of IL-17A in the BP pathogenesis: (i) IL-17A activated human neutrophils in vitro, (ii) inhibition of dermal-epidermal separation in cryosections of human skin incubated with anti-BP180 IgG and subsequently with anti-IL-17A IgG-treated leukocytes, (iii) close correlation of serum IL-17A levels and diseases activity in a mouse model of BP, (iv) IL17A-deficient mice were protected against autoantibody-induced BP, and (v) pharmacological inhibition of lL-17A reduced the induction of BP in mice. Our data give evidence for a pivotal role of IL-17A in the pathophysiology of BP and advocate IL-17A inhibition as potential novel treatment for this disease.

Original languageEnglish
JournalJournal of Autoimmunity
Pages (from-to)104-112
Number of pages9
Publication statusPublished - 01.01.2019


Dive into the research topics of 'IL-17A is functionally relevant and a potential therapeutic target in bullous pemphigoid'. Together they form a unique fingerprint.

Cite this