期刊
HEPATOLOGY
卷 50, 期 5, 页码 1606-1616出版社
WILEY-BLACKWELL
DOI: 10.1002/hep.23168
关键词
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资金
- National Key Basic Research Program of China [2007CB512807, 2007CB512403]
- National Natural Science Foundation of China [30721091]
- National 115 Key Project for Hepatitis B Research [2008ZX10002-008]
The beta 2 integrins play a key role in inflammation and immune responses. The beta 2 integrin CD11b has been shown recently to be important in the maintenance of tolerance; however, the underlying mechanisms remain to be fully understood. Natural killer (NK) cells are an important effector of innate immunity but are also a regulator of adaptive immune response. How the activating and inhibitory signals are balanced to determine NK cell function needs to be further identified. CD11b expression was dramatically up-regulated on NK cells once they matured and became activated; therefore, we investigated the role of inducible CD11b in the regulation of NK cells. Neutralizing anti-CD11b antibody enhanced cytotoxicity, interferon-gamma (IFN-gamma) and granzyme B production of Toll-like receptor 3 (TLR3)-triggered NK cells. CD11b-deficient NK cells stimulated with or without the TLR3 ligand polyinosinic:polycytidylic acid [poly(I:C)] exhibited more potent cytotoxicity, and higher production of IFN-gamma and granzyme B. Through in vivo depletion of NK cells and adoptive transfer of CD11b-deficient NK cells, we demonstrated that CD11b-mediated suppression of NK cell function was responsible for attenuation of poly(I:C)-induced acute hepatitis by CD11b. Conclusion: Our findings demonstrate that CD11b negatively regulates NK cell activation and thus attenuates poly(I:C)-induced acute hepatitis. Our study provides a new mechanistic explanation for maintenance of tolerance and control of inflammation by CD11b. (HEPATOLOGY 2009;50:1606-1616.)
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