IMPC: P2X7R dependent regulation of gut immunity

Lead Research Organisation: University of Manchester
Department Name: School of Biological Sciences


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Technical Summary

Our gut is a major site where infections can occur such as those caused by food poisoning. Having a healthy gut lining or barrier helps protect us against "bad" food borne bacteria. As well as protecting against bad bacteria and other infections, our gut is full of "good" bacteria - the microbiome- and these good bacteria help us digest our food and even keep our gut barrier healthy. Although these bacteria are helpful to us, if our body's defence system is not properly regulated we may react inappropriately to the bacteria which causes inflammatory bowel disease. The cells that line our gut, the epithelial cells, are really important to decide when the gut needs to ignore something that helps it, like the microbiome, and when we need to switch on the body's defence system to get rid of an infection. A big difference between an infection and the normal microbiome is that infections cause lots of damage to the gut. The damage causes lots of substances to be released and epithelial cells and defence cells can see these damage signals and then switch on the body's defence system. Equally, understanding how damage substances switch on the defence system can be useful in making drugs and vaccines work better for us and the animals around us. We will study how damage substances switch on or activate epithelial cells to make them respond to infection. We have identified that a receptor -P2X7R -in the gut lining can recognise the damage caused in infection and switch on the body's immune system. Immune cells also have this specialised receptor but our work suggests it works differently in immune cells to epithelial cells. We will use a transgenic mouse model that lacks this receptor only in the epithelium to dissect how the gut epithelium is responding to infectious stimuli and our friendly bacteria. Once we know how epithelial cells sense infection we can develop strategies to better tackle common infections and may even help diseases that cannot currently be cured such as IBD.


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Description Macrophage sensing of extracellular ATP during inflammation
Amount £578,600 (GBP)
Funding ID MR/T016043/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 03/2020 
End 03/2023
Description Pathways underlying resistance to infection: Dysregulation of gut homeostasis by damage associate signals.
Amount £90,000 (GBP)
Funding ID 1917196 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 09/2017 
End 09/2021
Title P2X7R-myeloid specific knockout mice. 
Description This grant was set to generate a P2X7R knock out mouse. We have generated mice that have P2X7R deleted specifically in the myeloid cells. 
Type Of Material Model of mechanisms or symptoms - mammalian in vivo 
Year Produced 2020 
Provided To Others? No  
Impact We hve not used it yet, as animals number are still low for a full experiment. However this will be a very useful tool to interrogate the role of P2X7 receptor in the inflammatory response, and specifically the direct role of the myeloid compartment in inflammatory responses. This mice strain will be essential for my future work funded by the MRC.