Elevated Levels of the Antimicrobial Peptide LL-37 in Hidradenitis Suppurativa Are Associated with a Th1/Th17 Immune Response

Hidradenitis suppurativa (HS) is an inflammatory skin disease with poorly understood immunopathogenic mechanisms. LL-37 is an antimicrobial peptide, which is transcribed from the CAMP (cathelicidin antimicrobial peptide) gene. Previous reports showed upregulated levels of CAMP and LL-37 in HS lesions, and therefore, the aim of this study was to compare levels of LL-37 in HS to other inflammatory skin diseases and to establish immunomodulatory functions of LL-37 in HS. We confirm an upregulation of the LL-37 peptide in lesional HS skin with comparable levels as in psoriasis patients and are able to positively correlate the presence of LL-37 in HS with the presence of T cells, macrophages, neutrophils, IFN-γ, IL-17, IL-23, TNF-α, IL-32 and IL-1β. Mechanistically, LL-37 boosts the proliferation of unspecifically activated CD4 T cells via an increased calcium signalling independent of antigen-presenting cells. Targeting LL-37 may therefore represent a new therapeutic option for the treatment of this recalcitrant disease, but it has to be kept in mind that LL-37 also has an antimicrobial function.