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SUMMARY:The role of the transcription factor T-bet in mucosal inflammation
  - Graham Lord\, MRC Centre for Transplantation\, King's College London
DTSTART:20130118T130000Z
DTEND:20130118T140000Z
UID:TALK41464@talks.cam.ac.uk
CONTACT:Dr Tennie Videler
DESCRIPTION:The nature of the interface of the immune system with the endo
 genous host microbiome is one of the most fundamental scientific questions
  currently being addressed. The predominant site of this interaction occur
 s at mucosal surfaces in the bowel\, although other sites such as the lung
  are also important. Dysregulation of this normally symbiotic relationship
  causes pathology\, most notably inflammatory bowel disease (IBD) and infl
 ammation-associated colonic cancer. Other diseases such as diabetes and ob
 esity have also been linked to an aberrant host-commensal relationship\, h
 ighlighting the critical importance of understanding this complex interact
 ion. \nWe have previously shown that the transcription factor (TF) T-bet (
 T-box expressed in T cells\, Tbx21) is a central mediator of this host-com
 mensal interaction via expression in colonic mucosal dendritic cells. The 
 molecular understanding of this model has been underpinned by the mapping 
 of transcription factor binding sites using genome wide location analysis\
 , identifying transcriptional derepression of TNF-α as a key initiating e
 vent.\nWe recently identified that the effector functions of a newly disco
 vered population of innate lymphoid cells (ILCs) are controlled by T-bet a
 nd have resolved the microbial drivers of mucosal inflammation at a specif
 ic bacteriological level. ILCs are thought to be one of the most important
  mediators of mucosal homeostasis in both health and disease and T-bet is 
 a critical molecular link between ILCs and dendritic cells (DCs) in the ca
 usation of IBD. The recent discovery that the genetic architecture predisp
 osing to IBD in humans maps to the innate immune system (specifically DCs)
  emphasizes the relevance of this work. \n
LOCATION:Sackler Lecture Theater on level 7 of the CIMR (Cambridge Institu
 te for Medical Research)
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