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SUMMARY:Novel targets to treat hyper-immune syndromes revealed by physiolo
 gic responses to DNA nanoparticles - Professor Andy Mellor\, Georgia Healt
 h Sciences University\, USA
DTSTART:20121008T113000Z
DTEND:20121008T123000Z
UID:TALK39761@talks.cam.ac.uk
CONTACT:Sue Griffin
DESCRIPTION:Strong associations between systemic autoimmunity and sustaine
 d type I interferon (IFNab) production by plasmacytoid dendritic cells (pD
 Cs) suggest that chronic exposure to TLR ligands that stimulate IFNab prod
 uction may incite autoimmunity.\n \nHowever\, IFNab also stimulates expres
 sion of the enzyme indoleamine 2\,3 dioxygenase (IDO) that blocks T cell i
 mmunity by activating Foxp3-lineage regulatory T cells (Tregs). IDO ablati
 on accelerates spontaneous autoimmune progression in lupus-prone MRL-lpr m
 ice and makes B6 mice susceptible to developing lupus-like syndromes follo
 wing chronic exposure to apoptotic cells\, indicating that IDO attenuates 
 lupus-progression. \n\nSystemic treatment with DNA nanoparticles induces r
 apid IFNab and IDO up-regulation\, and activates Tregs to suppress respons
 es to vaccines and immune-mediated arthritis. Nanoparticle cargo DNA is se
 nsed by a small population of splenic DCs via a cytoplasmic DNA sensing pa
 thway. \n\nThus the IDO pathway is a natural regulator of autoimmunity to 
 DNA\, and targeting this tolerogenic pathway may offer a novel approach to
  treating autoimmune syndromes such as SLE.\n
LOCATION:Lecture Theatre\, Department of Pathology\, Tennis Court Road
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