Science and Research

Neutrophil extracellular trap-associated RNA and LL37 enable self-amplifying inflammation in psoriasis

Psoriasis is an inflammatory skin disease with strong neutrophil (PMN) infiltration and high levels of the antimicrobial peptide, LL37. LL37 in complex with DNA and RNA is thought to initiate disease exacerbation via plasmacytoid dendritic cells. However, the source of nucleic acids supposed to start this initial inflammatory event remains unknown. We show here that primary murine and human PMNs mount a fulminant and self-propagating neutrophil extracellular trap (NET) and cytokine response, but independently of the canonical NET component, DNA. Unexpectedly, RNA, which is abundant in NETs and psoriatic but not healthy skin, in complex with LL37 triggered TLR8/TLR13-mediated cytokine and NET release by PMNs in vitro and in vivo. Transfer of NETs to naive human PMNs prompts additional NET release, promoting further inflammation. Our study thus uncovers a self-propagating vicious cycle contributing to chronic inflammation in psoriasis, and NET-associated RNA (naRNA) as a physiologically relevant NET component.

  • Herster, F.
  • Bittner, Z.
  • Archer, N. K.
  • Dickhofer, S.
  • Eisel, D.
  • Eigenbrod, T.
  • Knorpp, T.
  • Schneiderhan-Marra, N.
  • Loffler, M. W.
  • Kalbacher, H.
  • Vierbuchen, T.
  • Heine, H.
  • Miller, L. S.
  • Hartl, D.
  • Freund, L.
  • Schakel, K.
  • Heister, M.
  • Ghoreschi, K.
  • Weber, A. N. R.

Keywords

  • Adult
  • Animals
  • Antimicrobial Cationic Peptides
  • Cytokines/genetics/immunology
  • Extracellular Traps/genetics/*immunology
  • Female
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Middle Aged
  • Neutrophil Infiltration
  • Neutrophils/*immunology
  • Psoriasis/genetics/*immunology
  • RNA/genetics/immunology
  • Toll-Like Receptor 8/genetics/immunology
  • Young Adult
Publication details
DOI: 10.1038/s41467-019-13756-4
Journal: Nat Commun
Pages: 105 
Number: 1
Work Type: Original
Location: ARCN, TLRC
Disease Area: General Lung and Other
Partner / Member: FZB, UKHD
Access-Number: 31913271
See publication on PubMed

DZL Engagements

chevron-down