Chen Lab

The research focus of the Chen Laboratory is to understand the molecular mechanisms of atherosclerosis and vascular inflammation. We investigate the role of toll-like receptors and innate immunity in hypercholesterolemic mouse models of atherosclerosis, as well as the role of these innate immune receptors on Chlamydophila (C.) pneumonia-induced acceleration of atherosclerosis. C. pneumonia-induced acceleration of atherosclerosis was significantly dependent on NLRP3 and caspase-1. The Chen Lab discovered that C. pneumonia-induced extracellular IL-1β triggers a negative feedback loop to inhibit GPR109a and ABCA1 expression and cholesterol efflux leading to accumulation of intracellular cholesterol and foam cell formation. GPR109a and ABCA1 were both upregulated in plaque lesions in NLRP3 −/− mice in both hyperlipidemic and C. pneumonia infection models. Mature IL-1β and cholesterol may compete for access to the ABCA1 transporter to be exported from macrophages. C. pneumonia exploits this metabolic-immune crosstalk, which can be modulated by NLRP3 inhibitors to alleviate atherosclerosis.

The Chen Lab shows that RIP2 deficiency in CD4 + T cells resulted in chronic and severe interleukin-17A-mediated inflammation during C. pneumonia lung infection, increased T helper 17 cell formation in lungs of infected mice and accelerated atherosclerosis. Sex differences in the differential role of NLRP3 inflammasome is also being invested.

The Chen Laboratory is affiliated with the Infectious and Immunologic Diseases Research Center, Department of Biomedical Sciences and the Pediatrics Department.