Chaoxing Yang Laboratory
Our research goals are to identify T1D-specific biomarkers, to elucidate the mechanism of T1D initiation and progression during the early asymptomatic stage of the disease and to develop a non-invasive screening system for early T1D risk assessment.
It is generally accepted that T1D is caused by the autoimmune destruction of insulin-producing β cells, and that both genetics and the environment (such as viral infection) play etiological roles. We utilize a virus-inducible autoimmune diabetes rat model to investigate the pathogenesis of the disease. This model recapitulates many pathological characteristics observed in human T1D specimens. The highly consistent disease progression kinetics has given this model great advantages to overcome the unavoidable difficulties with human samples.
Our overall hypothesis of virus-induced autoimmune diabetes is as follows: 1) viral infection induces elevated and/or prolonged innate immune responses, systemically and locally (pancreas) in genetically susceptible individuals; 2) β cells undergo various cellular stress, one is ER stress, induced by cytokines, especially IFN; 3) stressed β cells may present auto-antigens through MHC class I antigen presentation pathway; 4) cytotoxic T cells are attracted by the signal sent by the stressed β cells and migrate to islets and start the active killing.