Increase in hepatic NKT cells in leukocyte cell-derived chemotaxin 2-deficient mice contributes to severe concanavalin A-induced hepatitis.
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.
Saito
Takeshi
T
Department of Bioactive Molecules, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
Okumura
Akinori
A
Watanabe
Hisami
H
Asano
Masahide
M
Ishida-Okawara
Akiko
A
Sakagami
Junko
J
Sudo
Katsuko
K
Hatano-Yokoe
Yoshimi
Y
Bezbradica
Jelena S
JS
Joyce
Sebastian
S
Abo
Toru
T
Iwakura
Yoichiro
Y
Suzuki
Kazuo
K
Yamagoe
Satoshi
S
D000818:Animals; D017304:Annexin A5 / Q000032:analysis; D003208:Concanavalin A / Q000633:toxicity*; D003602:Cytotoxicity, Immunologic; D053222:Fas Ligand Protein; D005434:Flow Cytometry; D006505:Hepatitis / Q000209:etiology*; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology*; D007958:Leukocyte Count; D008562:Membrane Glycoproteins / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL
D017304:Annexin A5; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; C491213:Lect2 protein, mouse; D008562:Membrane Glycoproteins; D003208:Concanavalin A