Activities Of Chemokines In Vivo

Niaid Extramural Activities

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Abstract

The purpose of the project is to investigate the biological roles of members of the chemokine family of cytokines by studying the actions of chemokines and their receptors in vivo, particularly in mouse models of infectious disease and inflammation. Chemokines and their receptors are critical for leukocyte trafficking. Our 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/IP-10 and Mig that are highly induced by gamma interferon. We discovered human CCR6, the receptor for the chemokine MIP-3alpha, and we have cloned the mouse analogue. We also cloned and characterized the human CCR9A and CCR9B, receptors for the chemokine TECK Part of this project is focused on using gene-targeted mice to investigate the roles of these ligand/receptor groups in models of immunity and inflammation in mice. Work in the last year has extensively characterized the expression of chemokines in Th2-biased and Th1-biased responses to the trematode Schistosoma mansoni in mice. Our findings suggest that there are patterns of coordinate chemokine expression characteristic of type1 and type 2 responses in vivo; that the cells recruited by chemokines may differ depending on the composition of peripheral populations in an immune response; and that changes in tissue expression of chemokines can be associated with changes in inflammation independent of the dominant pattern of differentation of antigen-specific T cells.differentiation are unaltered.