Abstract
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.
| Original language | English (US) |
|---|---|
| Article number | 105 |
| Journal | Nature communications |
| Volume | 11 |
| Issue number | 1 |
| DOIs | |
| State | Published - Dec 1 2020 |
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ASJC Scopus subject areas
- Chemistry(all)
- Biochemistry, Genetics and Molecular Biology(all)
- Physics and Astronomy(all)
Cite this
Neutrophil extracellular trap-associated RNA and LL37 enable self-amplifying inflammation in psoriasis. / Herster, Franziska; Bittner, Zsofia; Archer, Nathan K.; Dickhöfer, Sabine; Eisel, David; Eigenbrod, Tatjana; Knorpp, Thomas; Schneiderhan-Marra, Nicole; Löffler, Markus W.; Kalbacher, Hubert; Vierbuchen, Tim; Heine, Holger; Miller, Lloyd S.; Hartl, Dominik; Freund, Lukas; Schäkel, Knut; Heister, Martin; Ghoreschi, Kamran; Weber, Alexander N.R.
In: Nature communications, Vol. 11, No. 1, 105, 01.12.2020.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Neutrophil extracellular trap-associated RNA and LL37 enable self-amplifying inflammation in psoriasis
AU - Herster, Franziska
AU - Bittner, Zsofia
AU - Archer, Nathan K.
AU - Dickhöfer, Sabine
AU - Eisel, David
AU - Eigenbrod, Tatjana
AU - Knorpp, Thomas
AU - Schneiderhan-Marra, Nicole
AU - Löffler, Markus W.
AU - Kalbacher, Hubert
AU - Vierbuchen, Tim
AU - Heine, Holger
AU - Miller, Lloyd S.
AU - Hartl, Dominik
AU - Freund, Lukas
AU - Schäkel, Knut
AU - Heister, Martin
AU - Ghoreschi, Kamran
AU - Weber, Alexander N.R.
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85077590630&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85077590630&partnerID=8YFLogxK
U2 - 10.1038/s41467-019-13756-4
DO - 10.1038/s41467-019-13756-4
M3 - Article
C2 - 31913271
AN - SCOPUS:85077590630
VL - 11
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 105
ER -