Cathelicidin Antimicrobial Peptide LL-37 in Psoriasis Enables Keratinocyte Reactivity against TLR9 Ligands

• Published in: Journal of investigative dermatology Vol. 132; no. 1; pp. 135 - 143
• Main Authors: Morizane, Shin, Yamasaki, Kenshi, Mühleisen, Beda, Kotol, Paul F., Murakami, Masamoto, Aoyama, Yumi, Iwatsuki, Keiji, Hata, Tissa, Gallo, Richard L.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.01.2012; Nature Publishing Group; Elsevier Limited
• Subjects: Antimicrobial Cationic Peptides; Biological and medical sciences; Biopsy; Cathelicidins - genetics; Cathelicidins - immunology; Cathelicidins - metabolism; Cells, Cultured; CpG Islands - genetics; CpG Islands - immunology; Dermatology; DNA - immunology; DNA - pharmacology; Epidermal Cells; Gene Expression - immunology; Humans; Interferon Type I - genetics; Interferon Type I - immunology; Interferon Type I - metabolism; Interferon-beta - genetics; Interferon-beta - immunology; Interferon-beta - metabolism; Keratinocytes - cytology; Keratinocytes - physiology; Ligands; Medical sciences; Psoriasis - immunology; Psoriasis - physiopathology; Psoriasis. Parapsoriasis. Lichen; Toll-Like Receptor 9 - immunology; Toll-Like Receptor 9 - metabolism; Skin disease; Peptides; Psoriasis; Dermatology; Ligand; Keratinocyte; Antimicrobial agent
• ISSN: 0022-202X; 1523-1747
• DOI: 10.1038/jid.2011.259

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.