Selective expression of liver and activation-regulated chemokine (LARC) in intestinal epithelium in mice and humans.

The liver and activation-regulated chemokine (LARC), also termed MIP-3alpha and Exodus, is a novel human CC chemokine with a selective chemotactic activity for lymphocytes and dendritic cells. Here we describe genomic and cDNA clones encoding the murine orthologue of LARC (mLARC). The gene consists of four exons and three introns. The 5'-noncoding region of about 400 bp contains typical TATA and CAAT boxes but no other potential regulatory elements so far described. The cDNA encodes a CC chemokine of 97 amino acid residues with the highest homology to human LARC (64% amino acid identity). The 3'-noncoding region contains as many as five potential mRNA destabilization signals. mLARC was strongly and transiently induced in the murine monocytoid cell line J774 by lipopolysaccharide (LPS) but not by cytokines such as TNF-alpha, IFN-gamma, IL-1beta or IL-4. In normal mice, mLARC mRNA was expressed selectively in intestinal tissues such as small intestine and colon. Upon treatment with LPS, mLARC expression was enhanced in intestinal tissues and induced in some lymphoid tissues such as lymph nodes. Because of alternative splicing, there are two types of transcripts encoding mLARC and its variant mLARCvar with and without an N-terminal alanine in the mature protein, respectively. Both types of transcripts appeared to be expressed in various mouse tissues. In situ hybridization revealed that epithelial cells of intestinal tissues, especially those lining lymphoid follicles, expressed mLARC. Localization of LARC mRNA in epithelial cells was also demonstrated in a human appendix. Furthermore, mLARC was efficiently chemotactic for cells such as gammadelta type T cells in intestinal epithelium and naive B cells in Peyer's patches. Thus, in both humans and mice, LARC may be physiologically involved in formation and function of the mucosal lymphoid tissues by attracting lymphocytes and dendritic cells toward epithelial cells.