Introduction:
A number of gastrointestinal (GI) pathogens can increase the risk of colorectal cancer (CRC). However, the mechanism underpinning this association has only recently gained attention. In mice, GI pathogens have been shown to trigger Interleukin (IL)-17 mediated Signal Transducer and Activator of Transcription 3 (STAT3) activation in epithelial cells resulting in enhanced tumour progression. The primary source of IL-17 is thought to be a subset of CD4-positive T cells called T-helper (Th)-17 cells, which reside in the lamina propria. We aim to establish if a unique Th17 cell population can inadvertently drive CRC progression.
Method:
We have identified a unique population of Th17 cells in vitro through gene expression analysis. We have utilised multiple animal models to validate the pathogenicity of this cell population in vivo, ranging from a classic Th17 disease model of experimental autoimmune encephalomyelitis (EAE) to GI infections with mouse pathogens that trigger colitis. To further understand the role of this unique Th17 cell population in CRC, we have coupled genetic mouse models of CRC with C. rodentium infection, which triggers early CRC onset. Novel imaging platforms will allow us to track Th17 cells in tumours of individual live mice over the course of disease progression.
Results and Conclusion:
It is becoming increasingly accepted that viruses and bacteria can directly mutate epithelial cells, secrete mutagenic products, or trigger prolonged inflammation.Th17 cells are part of an inflammatory response to infection, with their numbers gradually increasing with tumour stage, and this increase is positively associated with poor prognosis in human CRC. We present the first evidence of a unique sub-population of Th17 cells that are present in the GI tract. Coupled to the knowledge that an estimated 20% of all cancers are caused by infectious agents, and the increasing epidemiological link between infections and CRC, there is an immediate need to better understand the host response to bacterial infections.