| Autor: |
Bork, Francesca, Greve, Carsten L, Youn, Christine, Chen, Sirui, N C Leal, Vinicius, Wang, Yu, Fischer, Berenice, Nasri, Masoud, Focken, Jule, Scheurer, Jasmin, Engels, Pujan, Dubbelaar, Marissa, Hipp, Katharina, Zalat, Baher, Szolek, Andras, Wu, Meng-Jen, Schittek, Birgit, Bugl, Stefanie, Kufer, Thomas A, Löffler, Markus W |
| Zdroj: |
EMBO Reports; Jul2024, Vol. 25 Issue 7, p2914-2949, 36p |
| Abstrakt: |
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. Synopsis: Neutrophil extracellular traps are key features of cellular innate immunity mediated by polymorphonuclear neutrophils. The NET-associated RNA (naRNA) composite danger-associated molecular pattern defines sterile NETs as self-propagating drivers of inflammation that amplify neutrophil activation. naRNA-LL37 amplifies NET formation in naive PMNs via a unique TLR8-NLRP3-caspase-1-gasdermin D-dependent pathway. Keratinocytes respond to naRNA with expression of psoriasis-related genes via atypical NOD2-RIPK signaling. The naRNA-LL37 'composite DAMP' is pre-stored in resting neutrophil granules. naRNA can drive transient skin inflammation via RNA receptors in vivo. Neutrophil extracellular traps are key features of cellular innate immunity mediated by polymorphonuclear neutrophils. The NET-associated RNA (naRNA)-LL37 composite danger-associated molecular pattern defines sterile NETs as self-propagating drivers of inflammation that amplify neutrophil activation. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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