HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Saito, T. Articles by Yamagoe, S. Search for Related Content PubMed PubMed Citation Articles by Saito, T. Articles by Yamagoe, S.

Increase in Hepatic NKT Cells in Leukocyte Cell-Derived Chemotaxin 2-Deficient Mice Contributes to Severe Concanavalin A-Induced Hepatitis¹

Takeshi Saito^*, Akinori Okumura^*, Hisami Watanabe, Masahide Asano^2,, Akiko Ishida-Okawara^*, Junko Sakagami, Katsuko Sudo, Yoshimi Hatano-Yokoe, Jelena S. Bezbradica^¶, Sebastian Joyce^¶, Toru Abo^||, Yoichiro Iwakura, Kazuo Suzuki^* and Satoshi Yamagoe^3,*

^* Department of Bioactive Molecules, National Institute of Infectious Diseases, Tokyo, Japan; Division of Cellular and Molecular Immunology, Center of Molecular Biosciences, University of Ryukyus, Okinawa, Japan; Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo, Japan; Department of Internal Medicine, Showa University, Tokyo, Japan; ^¶ Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232; and ^|| Department of Immunology, Niigata University School of Medicine, Niigata, Japan

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- was augmented in LECT2^–/– mice upon stimulation with -galactosylceramide, which specifically activates V14 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.

This article has been cited by other articles:

				H. Diao, K. Iwabuchi, L. Li, K. Onoe, L. Van Kaer, S. Kon, Y. Saito, J. Morimoto, D. T. Denhardt, S. Rittling, et al. Osteopontin regulates development and function of invariant natural killer T cells PNAS, October 14, 2008; 105(41): 15884 - 15889. [Abstract] [Full Text] [PDF]