The purpose of the project is to investigate the biological roles of members of the chemokine family of cytokines by studying chemokine actions in vivo, particularly in mouse models of infectious disease, inflammation, and angiogenesis. These experiments will provide important information for understanding in which therapeutic contexts in humans manipulating the chemokine system might be beneficial. This laboratory discovered two mouse chemokines, Crg-2 and Mig. Crg-2 is the mouse homologue of the human chemokine IP-10, and the murine Mig (MuMig) was used to identify a human homologue, HuMig. Crg-2/IP-10 and Mig are related interferon-gamma inducible chemokines that preferentially target lymphocytes, acting as chemotactic factors for activated T, activated B cells and natural killer cells. It is our hypothesis that these chemokines are important for recruiting T cells to sites of inflammation and perhaps for T cell: B cell cooperation as part of an immune response. In addition to studying Mig and Crg-2/IP-10 in a number of in vivo models of infection and inflammation, in some models the project will include a systematic evaluation of the expression of multiple chemokines in order to develop a more comprehensive understanding of the roles for chemokines in these reactions and to identify which are likely to be of principle importance within a particular context. Recently, the project has focused on models of experimental infections with the bacterium Francisella tularensis, the trematode Schistosoma mansoni, and vaccinia virus, on models of anti-tumor therapy, and on experimental autoimmune encephalitis. - Chemokines, Francisella tularensis, Schistosoma mansoni, vaccinia virus, experimental autoimmune encephalitis, cancer.
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