title: B7-H4-deficient mice display augmented neutrophil-mediated innate immunity.
abstract: B7-H4 is an immunoglobulin superfamily molecule and shown to be inhibitory for T-cell responses. To explore physiologic roles of B7-H4, we created B7-H4-deficient (KO) mice by genetic targeting. B7-H4KO mice are healthy and their T- and B-cell responses to polyclonal antigens are in normal range. However, B7-H4KO mice are more resistant to infection by Listeria monocytogenes than their littermates. Within 3 days after infection, bacterial colonies in livers and spleens are significantly lower than the controls, suggesting a role of B7-H4 in enhancing innate immunity. Further studies demonstrate that neutrophils increase in peripheral organs of B7-H4KO mice more so than their littermates but their bactericidal functions remain unchanged. Augmented innate resistance is completely dependent on neutrophils, even in the absence of adaptive immunity. In vitro B7-H4 inhibits the growth of bone marrow-derived neutrophil progenitors, suggesting an inhibitory function of B7-H4 in neutrophil expansion. Our results identify B7-H4 as a negative regulator of the neutrophil response to infection and provide a new target for manipulation of innate immunity.
authors.affiliation: Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
authors.forename: Gefeng
authors.initials: G
authors.lastname: Zhu
authors.forename: Mathew M
authors.initials: MM
authors.lastname: Augustine
authors.forename: Takeshi
authors.initials: T
authors.lastname: Azuma
authors.forename: Liqun
authors.initials: L
authors.lastname: Luo
authors.forename: Sheng
authors.initials: S
authors.lastname: Yao
authors.forename: Sudarshan
authors.initials: S
authors.lastname: Anand
authors.forename: A Cecilia
authors.initials: AC
authors.lastname: Rietz
authors.forename: Jiaqiang
authors.initials: J
authors.lastname: Huang
authors.forename: Haiying
authors.initials: H
authors.lastname: Xu
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Flies
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Flies
authors.forename: Koji
authors.initials: K
authors.lastname: Tamada
authors.forename: Marco
authors.initials: M
authors.lastname: Colonna
authors.forename: Jan M A
authors.initials: JM
authors.lastname: van Deursen
authors.forename: Lieping
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000382:microbiology; D018122:B7-1 Antigen / Q000235:genetics* / Q000276:immunology*; D001854:Bone Marrow Cells / Q000166:cytology; D039481:CD11b Antigen / Q000378:metabolism; D005260:Female; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D008088:Listeriosis / Q000276:immunology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology* / Q000382:microbiology; D010587:Phagocytosis / Q000276:immunology; D019707:Receptors, Chemokine / Q000378:metabolism; D016897:Respiratory Burst / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000382:microbiology; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1
chemical_list: D018122:B7-1 Antigen; D039481:CD11b Antigen; C503133:Gr-1 protein, mouse; D019707:Receptors, Chemokine; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1; C475824:Vtcn1 protein, mouse