Identifying molecular pathways that regulate T cell responses for the benefit of treating immune-mediated disease.
Research Interests of the Kuchroo Laboratory
The major focus of research in the laboratory is the regulation of T cell responses in the context of autoimmune disease. Particular focus is given to elucidating the role of cytokines and transcription factors in the differentiation of CD4+ T helper subsets in disease, the role of co-stimulatory and co-inhibitory receptors and their ligands in the regulation of autoreactive T cell responses, and the role of the TIM family of molecules in regulating effector and regulatory T cells.
The laboratory has primarily examined the autoreactive T cell response in experimental models of autoimmunity including Experimental autoimmune encephalomyelitis (EAE), type 1 diabetes, and colitis. For the study of EAE, the lab has created several models that are widely used by investigators in the field. These include models that harbor T cell reactivity to the myelin antigens myelin proteolipid protein (PLP) and myelin oligodendrocyte glycoprotein (MOG).
The laboratory has made several discoveries pertaining to the regulation of effector CD4+ T cell responses. These include the identification of Tim-3 (T cell Immunoglobulin and Mucin-3) as a cell surface molecule specifically expressed on CD4+ Th1 cells. The identification of Tim-3 led to the discovery of the TIM family of molecules, which includes Tim-1, Tim-2, Tim-3, and Tim-4. Tim-3 is now recognized as an important co-inhibitory receptor that dampens T cell responses in chronic viral diseases and cancer. The examination of how the different Tim molecules regulate T cell responses in disease conditions is an ongoing research effort in the laboratory. Other key discoveries made in the laboratory are the elucidation of the differentiation factors for IL-17-secreting Th17 cells, IL-9-secreting Th9 cells, and IL-10-secreting Tr1 cells, all of which can have a major influence on the development of autoimmunity and tissue inflammation. Elucidation of the transcriptional networks that give rise to these different T cell subsets and their impact on disease is another major research effort in the laboratory.