Cathelicidin antimicrobial peptide LL-37 in psoriasis enables keratinocyte reactivity against TLR9 ligands

Shin Morizane, Kenshi Yamasaki, Beda Mühleisen, Paul F. Kotol, Masamoto Murakami, Yumi Aoyama, Keiji Iwatsuki, Tissa Hata, Richard L. Gallo

Research output: Contribution to journalArticlepeer-review

127 Citations (Scopus)

Abstract

Here we show that keratinocytes in psoriatic lesional skin express increased Toll-like receptor (TLR) 9 that similarly localizes with elevated expression of the cathelicidin antimicrobial peptide LL-37. In culture, normal human keratinocytes exposed to LL-37 increased TLR9 expression. Furthermore, when keratinocytes were exposed to LL-37 and subsequently treated with TLR9 ligands, such as CpG or genomic DNA, they greatly increased production of type I IFNs. This response mimicked observations in the epidermis of psoriatic lesional skin as keratinocytes in psoriatic lesions produce greater amounts of IFN-Β than normal skin lacking LL-37. The mechanism for induction of type I IFNs in keratinocytes was dependent on TLR9 expression but not on a DNA-LL-37 complex. These findings suggest that keratinocytes recognize and respond to DNA and can actively participate in contributing to the immunological environment that characterizes psoriasis.

Original languageEnglish
Pages (from-to)135-143
Number of pages9
JournalJournal of Investigative Dermatology
Volume132
Issue number1
DOIs
Publication statusPublished - 2012 Jan

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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