University of Oxford, United Kingdom
Ischaemia-reperfusion injury (IRI) is the tissue damage caused after a period of a lack of oxygen. It causes damaging inflammation and can be a major health concern, but the underlying mechanisms remain elusive. Recent advances found a key role for iNKT cell activation, a type of innate T-lymphocyte. Mice with sickle cell disease, in which damaged red blood cells cause widely disseminated IRI, can be used as a scalable model of sterile, NKT-mediated inflammation.
We will investigate how the response to hypoxia and reperfusion causes NKT cell activation and tissue damage in sickle cell disease. We will explore two hypotheses: that the change in oxygen levels affects antigen presentation to NKT cells, or it acts on the differentiation into NKT cell types.
Our findings will identify metabolic mechanisms behind ischaemia.