title: The beta2 integrin CD11b attenuates polyinosinic:polycytidylic acid-induced hepatitis by negatively regulating natural killer cell functions.
abstract: The beta2 integrins play a key role in inflammation and immune responses. The beta2 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai, China.
authors.forename: Minggang
authors.initials: M
authors.lastname: Zhang
authors.forename: Yanmei
authors.initials: Y
authors.lastname: Han
authors.forename: Chaofeng
authors.initials: C
authors.lastname: Han
authors.forename: Sheng
authors.initials: S
authors.lastname: Xu
authors.forename: Yan
authors.initials: Y
authors.lastname: Bao
authors.forename: Zhubo
authors.initials: Z
authors.lastname: Chen
authors.forename: Yan
authors.initials: Y
authors.lastname: Gu
authors.forename: Dajing
authors.initials: D
authors.lastname: Xia
authors.forename: Xuetao
authors.initials: X
authors.lastname: Cao
mesh_terms: D000208:Acute Disease; D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D053804:Granzymes / Q000378:metabolism; D007369:Interferon Inducers / Q000009:adverse effects*; D007371:Interferon-gamma / Q000378:metabolism; D007694:Killer Cells, Natural / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011070:Poly I-C / Q000009:adverse effects*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D051196:Toll-Like Receptor 3 / Q000378:metabolism
chemical_list: D039481:CD11b Antigen; D007369:Interferon Inducers; D016755:Proto-Oncogene Proteins c-jun; C519703:TLR3 protein, mouse; D051196:Toll-Like Receptor 3; D007371:Interferon-gamma; D053804:Granzymes; D011070:Poly I-C