The Murine Chemokine CXCL11 (IFN-Inducible T Cell a Chemoattractant) Is an IFN-g- and Lipopolysaccharide- Inducible Glucocorticoid-Attenuated Response Gene Expressed in Lung and Other Tissues During Endotoxemia

A new murine chemokine was identified in a search for glucocorticoid-attenuated response genes induced in the lung during endotoxemia. The first 73 residues of the predicted mature peptide are 71% identical and 93% similar to human CXCL11/IFNinducible T cell a chemoattractant (I-TAC) (alias b-R1, H174, IFN-inducible protein 9 (IP-9), and SCYB9B). The murine chemokine has six additional residues at the carboxyl terminus not present in human I-TAC. Identification of this cDNA as murine CXCL11/I-TAC is supported by phylogenetic analysis and by radiation hybrid mapping of murine I-TAC (gene symbol Scyb11) to mouse chromosome 5 close to the genes for monokine induced by IFN-g (MIG) and IP10. Murine I-TAC mRNA is induced in RAW 264.7 macrophages by IFN-g or LPS and is weakly induced by IFN-ab. IFN-g induction of murine I-TAC is markedly enhanced by costimulation with LPS or IL-1b in RAW cells and by TNF-a in both RAW cells and Swiss 3T3 fibroblasts. Murine I-TAC is induced in multiple tissues during endoxemia, with strongest expression in lung, heart, small intestine, and kidney, a pattern of tissue expression different from those of MIG and IP10. Peak expression of I-TAC message is delayed compared with IP10, both in lung after i.v. LPS and in RAW 264.7 cells treated with LPS or with IFN-g. Pretreatment with dexamethasone strongly attenuates both IFN-g-induced I-TAC expression in RAW cells and endotoxemia-induced I-TAC expression in lung and small intestine. The structural and regulatory similarities of murine and human I-TAC suggest that mouse models will be useful for investigating the role of this chemokine in human biology and disease. The Journal of Immunology, 2000, 164: 6322–6331.