NKG2D-retinoic acid early inducible-1 recognition between natural killer cells and Kupffer cells in a novel murine natural killer cell-dependent fulminant hepatitis.
Increasing evidence suggests the contribution of natural killer (NK) cells to pathogenesis of human hepatitis, but the detailed mechanisms have yet to be clearly elucidated. In this study, injection of polyinosinic:polycytidylic acid (poly I:C) and D-galactosamine (D-GalN) was used to establish a novel murine fulminant hepatitis model: results showed that predepletion of either NK cells or Kupffer cells could completely abolish the liver injury. Injection of poly I:C/D-GalN into mice could promote tumor necrosis factor-alpha production and surface retinoic acid early inducible-1 (Rae1) protein expression by Kupffer cells, which then activated NK cells to produce interferon-gamma via NKG2D-Rae1 recognition. NK cell-derived interferon-gamma and Kupffer cell-derived tumor necrosis factor-alpha synergistically mediated the severe liver injury. Moreover, Kupffer cell-derived interleukin-12 and interleukin-18 were also found to improve cross talk between NK cells and Kupffer cells.


CONCLUSIONS
These results provide the first in vivo evidence that NKG2D/ligand interaction is involved in the synergic effects of NK cells and Kupffer cells on acute liver injury.
Hou
Xin
X
Institute of Immunology, Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, China.
Zhou
Rongbin
R
Wei
Haiming
H
Sun
Rui
R
Tian
Zhigang
Z
D000818:Animals; D002450:Cell Communication; D002478:Cells, Cultured; D018920:Coculture Techniques; D004195:Disease Models, Animal; D005688:Galactosamine / Q000009:adverse effects; D006505:Hepatitis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D020382:Interleukin-18 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000378:metabolism* / Q000473:pathology*; D007728:Kupffer Cells / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000378:metabolism*; D034521:Nuclear Matrix-Associated Proteins / Q000378:metabolism*; D029543:Nucleocytoplasmic Transport Proteins / Q000378:metabolism*; D011070:Poly I-C / Q000009:adverse effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D020382:Interleukin-18; C527086:Klrk1 protein, mouse; D055655:NK Cell Lectin-Like Receptor Subfamily K; D034521:Nuclear Matrix-Associated Proteins; D029543:Nucleocytoplasmic Transport Proteins; C490521:Rae1 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D005688:Galactosamine; D007371:Interferon-gamma; D011070:Poly I-C