Cathelicidin Antimicrobial Peptide LL37 Induces TLR8 and Amplifies IL-36γ and IL-17C in Human Keratinocytes

LL37 is produced by skin injury and Bacterial infection and plays an important role in the early stages of psoriasis. In particular, the intracellular receptors TLRs 3, 7, 8, and 9 are thought to be involved in the pathogenesis of psoriasis in conjunction with LL37, but the interaction between TLR7/8 and LL37 in keratinocytes remains unclear. This study aimed to clarify the relationship between LL37 and TLR7/8 in keratinocytes and their involvement in the pathogenetic pathways seen in psoriasis using cultured keratinocytes and psoriasis patient skin samples. TLR7/8 was induced by LL37 in keratinocytes. TLR8 but not TLR7 functionally induced many psoriasis-related molecules, whereas IL-17C was not altered by the blockade of TLR7/8. While co-stimulated of LL37 with self-RNA/DNA did not show any interaction, LL37 itself would promote psoriasis-related genes. IL-36 receptor antagonistic antibody suppressed IL-17C induced by LL37. In psoriatic epidermis, LL37, TLRs, IL-17C, and IL-36γ expressions were increased and co-expressed with each Other. Thus, we concluded that LL37 activates TLR8 in keratinocytes and induces IL-17C via induction of IL-36γ. Regulation of TLR8 or LL37 in keratinocytes could be a potential therapeutic strategy for psoriatic inflammation.