TOKITA Daisuke    Department   School of Medicine(Tokyo Women's Medical University Hospital), School of Medicine    Position
Article types	Original article
Language	English
Peer review	Peer reviewed
Title	Liver NK cells expressing TRAIL are toxic against self hepatocytes in mice.
Journal	Formal name：Hepatology (Baltimore, Md.) Abbreviation：Hepatology ISSN code：02709139/02709139
Domestic / Foregin	Foregin
Volume, Issue, Page	39(5),pp.1321-31
Author and coauthor	Ochi Makoto, Ohdan Hideki, Mitsuta Hiroshi, Onoe Takashi, Tokita Daisuke, Hara Hidetaka, Ishiyama Kohei, Zhou Wendy, Tanaka Yuka, Asahara Toshimasa
Publication date	2004/05
Summary	Although it is known that activation of natural killer (NK) cells causes liver injury, the mechanisms underlying NK cell-induced killing of self-hepatocytes are not clear. We demonstrated that liver NK cells have cytotoxicity against normal syngeneic hepatocytes in mice. Polyinosinic-polycytidylic acid (poly I:C) treatment enhanced hepatocyte toxicity of liver NK cells but not that of spleen NK cells. Unlike NK cells in other tissues, approximately 30%-40% of liver NK cells constitutively express tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). An in vitro NK cell cytotoxic assay revealed that hepatocyte toxicity of liver NK cells from both naïve and poly I:C-treated mice was inhibited partially by an anti-TRAIL monoclonal antibody (mAb) alone and completely by the combination with anti-Fas ligand (FasL) mAb and a perforin inhibitor, concanamycin A, indicating contribution of TRAIL to NK cell-mediated hepatocyte toxicity. The majority of TRAIL(+) NK cells lacked expression of Ly-49 inhibitory receptors recognizing self-major histocompatibility complex class I, indicating a propensity to targeting self-hepatocytes. Poly I:C treatment significantly upregulated the expression of Ly-49 receptors on TRAIL(-) NK cells. This might be a compensatory mechanism to protect self-class I-expressing cells from activated NK cell-mediated killing. However, such compensatory alteration was not seen at all in the TRAIL(+) NK cell fraction. Thus, liver TRAIL(+) NK cells have less capacity for self-recognition, and this might be involved in NK cell-dependent self-hepatocyte toxicity. In conclusion, our findings are consistent with a model in which TRAIL-expressing NK cells play a critical role in self-hepatocyte killing through poor recognition of MHC.
DOI	10.1002/hep.20204
PMID	15122761