Research Abstract:
The goal of my laboratory is to understand the processes that regulate immune responses. Our studies have concentrated on the molecular basis of immune tolerance and how apoptotic cells tolerize the immune response. We have shown that apoptosis induced by death receptors induces immune tolerance via the induction of T regulatory cells. Our studies try to understand the molecular basis of this type if immune regulation using biochemistry and gene targeting technology. Currently we are studying what it is about apoptosis, per se, that reprograms dendritic cells away from their ability to activate immunity to potent inducers of immune tolerance. Studies have shown that oxidative conditions created during apoptosis detemine the outcome of an immune response taking place in the presence of dead cells. Specifically, reactive oxygen species producted during degradation of the mitochondria during apoptosis oxidizes danger signals such as HMGB1 destroying their function. These studies have important implications in cancer immunobiology, autoimmunity, and resistance to infection.
The laboratory also studies the role of TNF and TNFR family members in controlling angiogenesis. Uncontrolled growth of new vessels in the eye is a significant cause of visual loss in patients with diabetes and macular degeneration. We have found that FasL expressed in the retina prevents the growth of new vessels by interacting with Fas+endothelial cells on growing vessels. We are currently examining the role of immune privielge and FasL in controlling angiogenesis.
Selected Publications:
Yin J, Ferguson TA. Identification of an IFN-gamma Producing Neutrophil Early in the Response to Listeria monocytogenes. J Immunol. 2009 182: 7069-7073
Kazama H, Ricci J-E, Herndon JM, Hoppe G, Green DR, Ferguson TA. Immune tolerance by apoptotic cells requires caspase dependent oxidation of HMGB1. Immunity 2008 29:21-31.
Griffith TS, Kazama H, VanOosten RL, Earle JK, Herndon JM, Green DR, Ferguson TA. Infectious tolerance induced by apoptotic cells is mediated by TRAIL. J Immunol 2007 178:2679-2687.
Apte RS, Richter J, Herndon JM, Ferguson TA. Macrophages inhibit neovascularization in a murine model of age related macular degeneration. PLoS medicine. August 2006. http://dx.doi.org/10.1371/journal.pmed.0030310.
Unsinger J, Herndon JM, Davis C, Hotchkiss RT, Ferguson TA. The role of T cell receptor engagement in sepsis induced T cell apoptosis. J Immunol 2006 177:7968-7973.
Last Updated: 08/27/2009 |