The role of the transcription factor T-bet in mucosal inflammation

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• Graham Lord, MRC Centre for Transplantation, King's College London
• Friday 18 January 2013, 13:00-14:00
• Sackler Lecture Theater on level 7 of the CIMR (Cambridge Institute for Medical Research).

If you have a question about this talk, please contact Dr Tennie Videler.

hosted by Andrew McKenzie.

The nature of the interface of the immune system with the endogenous host microbiome is one of the most fundamental scientific questions currently being addressed. The predominant site of this interaction occurs 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 inflammation-associated colonic cancer. Other diseases such as diabetes and obesity have also been linked to an aberrant host-commensal relationship, highlighting the critical importance of understanding this complex interaction. We have previously shown that the transcription factor (TF) T-bet (T-box expressed in T cells, Tbx21) is a central mediator of this host-commensal 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 event. We recently identified that the effector functions of a newly discovered population of innate lymphoid cells (ILCs) are controlled by T-bet and have resolved the microbial drivers of mucosal inflammation at a specific 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 causation of IBD . The recent discovery that the genetic architecture predisposing to IBD in humans maps to the innate immune system (specifically DCs) emphasizes the relevance of this work.

This talk is part of the Immunology in medicine series.

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