Silencing of IL-17 modulates inflammatory and antimicrobial defense responses mediated by Propionibacterium acnes (HUM7P.291)

Abstract

Abstract Inflammation resulting from immune responses targeting Propionibacterium acnes plays a significant role in acne pathogenesis. We demonstrate that IL-17-expressing cells are present in skin biopsies from acne patients, and that P. acnes is a potent inducer of Th17-related cytokines, including IL-17 (inflammatory) and IL-22 (antimicrobial defense and tissue repair). Here we investigated whether silencing of IL-17 and IL-22 modulates Th17-related inflammatory and antimicrobial responses mediated by P. acnes. P. acnes stimulated peripheral blood mononuclear cells (PBMCs) demonstrated elevated expression of antimicrobial peptides (AMPs); psoriasin, cathelicidins, defensins, and antimicrobial chemokines; CXCL-1/-9/-10/-11 and CCL15 expression. siRNA-mediated knockdown of IL-17 led to loss of capacity to express and secrete IL-17, IL-22 and AMPs upon P. acnes stimulation. However, knocking-down IL-22 alone led to decreased AMP expression, but had no effect on the expression of genes known to directly signal Th17 responses including IL-17A, RORα and RORc. Both IL-17 and IL-22 were required for antimicrobial chemokines CXCL1 and CXCL10 expression, but not CXCL9, CXCL11 and CCL15. Importantly, IL-22 may play a role in modulating the IL-17-driven chronic inflammatory responses initiated by P. acnes and that treatments targeting the IL-17 pathway may be effective tools for acne therapy.