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SUMMARY:naRNA is a canonical neutrophil extracellular trap (NET) component
  and novel inflammation-amplifying composite DAMP - Prof Alex Weber\, Univ
 ersity of Tübingen\, Germany. Hosted by Prof Nick Gay
DTSTART:20220817T133000Z
DTEND:20220817T143000Z
UID:TALK177416@talks.cam.ac.uk
CONTACT:108497
DESCRIPTION:Neutrophil extracellular traps (NETs) have emerged as a key fe
 ature of\ncellular innate immunity mediated by polymorphonuclear neutrophi
 ls (PMNs)\, the primary leukocyte population in humans. Forming web-like s
 tructures composed of DNA\, histones\, and antimicrobial proteins\, NETs t
 rap and kill microbial invaders and thus enhance host defense. However\, t
 hey have also been linked to inflammatory states\, e.g. in atherosclerosis
  or psoriasis. Whilst DNA has been in focus as a primary structural compon
 ent of NETs\, we here characterize naRNA (NET-associated RNA)\, as a new c
 anonical\, abundant\, and largely unexplored NET component. naRNA decorate
 d all types of NETs in complex with the antimicrobial peptide LL37. In fac
 t\, naRNA was preassociated with LL37 intracellularly as a ‘composite’
  danger-associated molecular pattern (DAMP) prior to neutrophil activation
 . Externalized\, naRNA propagated NET formation in naïve PMN\, dependent 
 on TLR8 in humans and Tlr13 in mice\, in vitro and in vivo. naRNA-TLR8/Tlr
 13 signaling contributed significantly to the highly sensitive pro-inflamm
 atory response of both tissue cells\, like keratinocytes\, and other immun
 e cell types\, such as macrophages. Those responses could be blocked by in
 hibition and genetic ablation of RNA receptors or RNase treatment. Importa
 ntly\, in vivo naRNA strongly drove skin inflammation whereas genetic abla
 tion of RNA sensing drastically ameliorated skin inflammation in the imiqu
 imod psoriasis model. Our data highlight naRNA as a novel composite DAMP s
 ignaling and amplifying neutrophil activation. Moreover\, naRNA emerges as
  the likely driver of inflammation in conditions previously linked to NETs
  and extracellular RNA\, suggesting blockade of TLRmediated RNA sensing as
  potential new intervention target.
LOCATION:Seminar Room\, Sanger Building\, 80\, Tennis Court Road\, Cambrid
 ge\, CB2 1GA
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