Neutrophil extracellular trap-associated RNA and LL37 enable self-amplifying inflammation in psoriasis
| Autor: | Dominik Hartl, Thomas Knorpp, Hubert Kalbacher, Knut Schäkel, Nicole Schneiderhan-Marra, Holger Heine, Lloyd S. Miller, Sabine Dickhöfer, Zsofia Bittner, Tatjana Eigenbrod, Kamran Ghoreschi, Tim Vierbuchen, Markus W. Löffler, Nathan K. Archer, Franziska Herster, Martin Heister, Alexander N.R. Weber, Lukas Freund, David Eisel |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Neutrophils medicine.medical_treatment General Physics and Astronomy Extracellular Traps chemistry.chemical_compound Mice 0302 clinical medicine lcsh:Science Multidisciplinary Chemistry Chronic inflammation Middle Aged Skin diseases Cytokine Neutrophil Infiltration 030220 oncology & carcinogenesis Cytokines Female medicine.symptom Adult Science Inflammation General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Young Adult Cathelicidins Psoriasis medicine Animals Humans RNA General Chemistry Neutrophil extracellular traps TLR8 medicine.disease Toll-like receptors Mice Inbred C57BL 030104 developmental biology Toll-Like Receptor 8 Immunology Nucleic acid lcsh:Q DNA Antimicrobial Cationic Peptides |
| Zdroj: | Nature Communications Nature Communications, Vol 11, Iss 1, Pp 1-13 (2020) |
| ISSN: | 2041-1723 |
| Popis: | 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. Antimicrobial peptide LL37 can bind nucleic acids and potentiate their sensing by endosomal TLRs. Here the authors show that LL37 binds to RNA from neutrophil extracellular traps (NETs), which amplifies inflammation and production of more LL37 and NETs via TLR8/13, suggesting that LL37 contribution to psoriasis may be fueled by NET-associated RNA. |
| Databáze: | OpenAIRE |
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