Cationic antimicrobial peptides in psoriatic skin cooperate to break innate tolerance to self-DNA

Eur J Immunol. 2015 Jan;45(1):203-13. doi: 10.1002/eji.201344277. Epub 2014 Nov 13.


Psoriasis is a T-cell-mediated skin autoimmune disease characterized by the aberrant activation of dermal dendritic cells (DCs) and the sustained epidermal expression of antimicrobial peptides. We have previously identified a link between these two events by showing that the cathelicidin antimicrobial peptide LL37 has the ability to trigger self-nucleic acid mediated activation of plasmacytoid DCs (pDCs) in psoriatic skin. Whether other cationic antimicrobial peptides exert similar activities is unknown. By analyzing heparin-binding HPLC fractions of psoriatic scales, we found that human beta-defensin (hBD)2, hBD3, and lysozyme are additional triggers of pDC activation in psoriatic skin lesions. Like LL37, hBD2, hBD3, and lysozyme are able to condense self-DNA into particles that are endocytosed by pDCs, leading to activation of TLR9. In contrast, other antimicrobial peptides expressed in psoriatic skin including elafin, hBD1, and psoriasin (S100A7) did not show similar activities. hBD2, hBD3, and lysozyme were detected in psoriatic skin lesions in the vicinity of pDCs and found to cooperate with LL37 to induce high levels of IFN production by pDCs, suggesting their concerted role in the pathogenesis of psoriasis.

Keywords: Antimicrobial peptides; Plasmacytoid DC; Psoriasis; Skin; Toll-like receptor.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimicrobial Cationic Peptides
  • Cathelicidins / genetics
  • Cathelicidins / immunology
  • DNA / genetics
  • DNA / immunology
  • Dendritic Cells / immunology*
  • Dendritic Cells / pathology
  • Gene Expression Regulation
  • Humans
  • Langerhans Cells / immunology*
  • Langerhans Cells / pathology
  • Muramidase / genetics
  • Muramidase / immunology*
  • Psoriasis / genetics
  • Psoriasis / immunology*
  • Psoriasis / pathology
  • Self Tolerance
  • Signal Transduction
  • Skin / immunology*
  • Skin / pathology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / pathology
  • Toll-Like Receptor 9 / genetics
  • Toll-Like Receptor 9 / immunology
  • beta-Defensins / genetics
  • beta-Defensins / immunology*


  • Antimicrobial Cationic Peptides
  • Cathelicidins
  • DEFB103A protein, human
  • DEFB4A protein, human
  • TLR9 protein, human
  • Toll-Like Receptor 9
  • beta-Defensins
  • DNA
  • Muramidase