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Leukocyte cell-derived chemotaxin 2 (LECT2) was originally identified for its possible chemotactic activity against human neutrophils in vitro. It is a 16-kDa protein that is preferentially expressed in the liver. Its homologues have been widely identified in many vertebrates. Current evidence suggests that LECT2 may be a multifunctional protein like cytokines. However, the function of LECT2 in vivo remains unclear. To elucidate the role of this protein in vivo, we have generated LECT2-deficient (LECT2(-/-)) mice. We found that the proportion of NKT cells in the liver increased significantly in LECT2(-/-) mice, although those of conventional T cells, NK cells, and other cell types were comparable with those in wild-type mice. Consistent with increased hepatic NKT cell number, the production of IL-4 and IFN-gamma was augmented in LECT2(-/-) mice upon stimulation with alpha-galactosylceramide, which specifically activates Valpha14 NKT cells. In addition, NKT cell-mediated cytotoxic activity against syngeneic thymocytes increased in hepatic mononuclear cells obtained from LECT2(-/-) mice in vitro. Interestingly, the hepatic injury was exacerbated in LECT2(-/-) mice upon treatment with Con A, possibly because of the significantly higher expression of IL-4 and Fas ligand. These results suggest that LECT2 might regulate the homeostasis of NKT cells in the liver and might be involved in the pathogenesis of hepatitis.

Original publication

DOI

10.4049/jimmunol.173.1.579

Type

Journal article

Journal

Journal of immunology (Baltimore, Md. : 1950)

Publication Date

07/2004

Volume

173

Pages

579 - 585

Addresses

Department of Bioactive Molecules, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.

Keywords

Killer Cells, Natural, Animals, Mice, Inbred C57BL, Mice, Hepatitis, Intercellular Signaling Peptides and Proteins, Annexin A5, Membrane Glycoproteins, Concanavalin A, Leukocyte Count, Flow Cytometry, Cytotoxicity, Immunologic, Fas Ligand Protein