naRNA-LL37 composite DAMPs define sterile NETs as self-propagating drivers of inflammation.
EMBO Rep
; 25(7): 2914-2949, 2024 Jul.
Article
em En
| MEDLINE
| ID: mdl-38783164
ABSTRACT
Neutrophil extracellular traps (NETs) are a key antimicrobial feature of cellular innate immunity mediated by polymorphonuclear neutrophils (PMNs). NETs counteract microbes but are also linked to inflammation in atherosclerosis, arthritis, or psoriasis by unknown mechanisms. Here, we report that NET-associated RNA (naRNA) stimulates further NET formation in naive PMNs via a unique TLR8-NLRP3 inflammasome-dependent pathway. Keratinocytes respond to naRNA with expression of psoriasis-related genes (e.g., IL17, IL36) via atypical NOD2-RIPK signaling. In vivo, naRNA drives temporary skin inflammation, which is drastically ameliorated by genetic ablation of RNA sensing. Unexpectedly, the naRNA-LL37 'composite damage-associated molecular pattern (DAMP)' is pre-stored in resting neutrophil granules, defining sterile NETs as inflammatory webs that amplify neutrophil activation. However, the activity of the naRNA-LL37 DAMP is transient and hence supposedly self-limiting under physiological conditions. Collectively, upon dysregulated NET release like in psoriasis, naRNA sensing may represent both a potential cause of disease and a new intervention target.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Catelicidinas
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Armadilhas Extracelulares
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Alarminas
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Inflamação
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Neutrófilos
Limite:
Animals
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Humans
Idioma:
En
Revista:
EMBO Rep
/
EMBO rep
/
EMBO reports
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Alemanha