BEGIN:VCALENDAR
VERSION:2.0
PRODID:-//Talks.cam//talks.cam.ac.uk//
X-WR-CALNAME:Talks.cam
BEGIN:VEVENT
SUMMARY:naRNA is a canonical neutrophil extracellular trap (NET) component
  and novel inflammation-amplifying composite DAMP - Alex Weber\, Professor
  of Innate Immunity at the University of Tübingen\, Germany
DTSTART:20220817T133000Z
DTEND:20220817T150000Z
UID:TALK177410@talks.cam.ac.uk
CONTACT:Nicholas Gay
DESCRIPTION:Neutrophil extracellular traps (NETs) have emerged as a key fe
 ature of cellular innate immunity mediated by polymorphonuclear neutrophil
 s (PMNs)\, the primary leukocyte population in humans. Forming web-like st
 ructures composed of DNA\, histones\, and antimicrobial proteins\, NETs tr
 ap and kill\nmicrobial 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\,\nand largely unexplored NET component. naRNA decorat
 ed all types of NETs in complex with the antimicrobial peptide LL37. In fa
 ct\, naRNA was preassociated with LL37 intracellularly as a ‘composite
 ’ danger-associated molecular pattern (DAMP) prior to neutrophil activat
 ion. Externalized\, naRNA propagated NET formation in naïve PMN\, depende
 nt on TLR8 in humans and Tlr13 in mice\, in vitro and in vivo. naRNA-TLR8/
 Tlr13 signaling contributed significantly to the highly sensitive pro-infl
 ammatory response of both tissue cells\, like keratinocytes\, and other im
 mune cell types\, such as macrophages.Those responses could be blocked by 
 inhibition and genetic ablation of RNA receptors or RNase treatment. Impor
 tantly\, in vivo naRNA strongly drove skin inflammation whereas genetic ab
 lation of RNA sensing drastically ameliorated skin inflammation in the imi
 quimod psoriasis model. Our data highlight naRNA as a novel composite DAMP
  signaling and amplifying neutrophil activation.\nMoreover\, naRNA emerges
  as the likely driver of inflammation in conditions previously linked to N
 ETs and extracellular RNA\, suggesting blockade of TLRmediated RNA sensing
  as potential new intervention target.
LOCATION:Department of Biochemistry\, Sanger Building\, Perham Seminar Roo
 m
END:VEVENT
END:VCALENDAR