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

The liver and activation-regulated chemokine (LARC), also termed MIP-3 alph a and Exodus, is a novel human CC chemokine with a selective chemotactic ac tivity for lymphocytes and dendritic cells. Here we describe genomic and cD NA 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 c ontains typical TATA and CAAT boxes but no other potential regulatory eleme nts so far described. The cDNA encodes a CC chemokine of 97 amino acid resi dues with the highest homology to human LARC (64 % amino acid identity). Th e 3'-noncoding region contains as many as five potential mRNA destabilizati on signals, mLARC was strongly and transiently induced in the murine monocy toid cell line J774 by lipopolysaccharide (LPS) but not by cytokines such a s TNF-alpha, IFN-gamma, IL-1 beta or IL-4. In normal mice, mLARC mRNA was e xpressed selectively in intestinal tissues such as small intestine and colo n. Upon treatment with LPS, mLARC expression was enhanced in intestinal tis sues and induced in some lymphoid tissues such as lymph nodes. Because of a lternative splicing, there are two types of transcripts encoding mLARC and its variant mLARCvar with and without an N-terminal alanine in the mature p rotein, respectively. Both types of transcripts appeared to be expressed in various mouse tissues. In situ hybridization revealed that epithelial cell s of intestinal tissues, especially those lining lymphoid follicles, expres sed mLARC. Localization of LARC mRNA in epithelial cells was also demonstra ted in a human appendix. Furthermore, mLARC was efficiently chemotactic for cells such as gamma delta type T cells in intestinal epithelium and naive B cells in Peyer's patches. Thus, in both humans and mice, LARC may be phys iologically involved in formation and function of the mucosal lymphoid tiss ues by attracting lymphocytes and dendritic cells toward epithelial cells.