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B7-H4–deficient mice display augmented neutrophil-mediated innate immunity

Citation

Zhu, G and Augustine, MM and Azuma, T and Luo, L and Yao, S and Anand, S and Rietz, AC and Huang, J and Xu, H and Flies, AS and Tamada, K and Colonna, M and van Duersen, JMA and Chen, L, B7-H4-deficient mice display augmented neutrophil-mediated innate immunity, Blood, 113, (8) pp. 1759-1767. ISSN 0006-4971 (2008) [Refereed Article]

Copyright Statement

Copyright 2009 The American Society of Hematology

DOI: doi:10.1182/blood-2008-01-133223

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 monocytogenesthantheirlittermates.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.

Item Details

Item Type:Refereed Article
Keywords:B7-H4
Research Division:Medical and Health Sciences
Research Group:Immunology
Research Field:Cellular Immunology
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Immune System and Allergy
Author:Flies, AS (Dr Andy Flies)
ID Code:102797
Year Published:2008
Web of Science® Times Cited:48
Deposited By:Menzies Institute for Medical Research
Deposited On:2015-09-07
Last Modified:2015-10-06
Downloads:0

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