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/CXCL10 and Mig/CXCL9 that are highly induced by gamma interferon. We discovered human CCR6, the receptor for the chemokine MIP-3alpha/CCL20, and we have cloned the mouse analogue. We also cloned and characterized the human CCR9A and CCR9B, receptors for the chemokine TECK/CCL25. 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 focused on the analysis of mice with targeted deletion of the genes for CXCL9 and for CCR9. For CXCL9 we have demonstrated functional expression of its receptor, CXCR3, on activated B cells and an unexpected role in supporting antibody production against a bacterial pathogen. For CCR9, we have demonstrated a role in supporting thymocyte development and in maintaining gamma/delta T cells in the gut.