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 toll-like
receptors (TLR)3, TLR7, TLR8, and TLR9 are thought to be involved in the pathogenesis
of psoriasis in conjunction with LL37, but the interaction between TLR7/8 and LL37
in keratinocytes (KCs) remains unclear. This study aimed to clarify the relationship
between LL37 and TLR7/8 in KCs and their involvement in the pathogenetic pathways
seen in psoriasis using cultured KCs and skin samples of patients with psoriasis.
TLR7/8 was induced by LL37 in KCs. TLR8 but not TLR7 functionally induced many psoriasis-related
molecules, whereas IL-17C was not altered by the blockade of TLR7/8. Although costimulation
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 coexpressed with each other. Thus, we concluded that LL37 activates TLR8 in KCs
and induces IL-17C through the induction of IL-36γ. Regulation of TLR8 or LL37 in
KCs could be a potential therapeutic strategy for psoriatic inflammation.
Abbreviations:
DC (dendritic cell), dsRNA (double-stranded RNA), KC (keratinocyte), NHEK (normal human epidermal keratinocyte), TLR (toll-like receptor)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: December 06, 2022
Accepted:
October 26,
2022
Received in revised form:
October 25,
2022
Received:
February 22,
2022
accepted manuscript published online XXX; corrected proof published online XXXPublication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2022 The Authors. Published by Elsevier, Inc. on behalf of the Society for Investigative Dermatology.
