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B7-H4–deficient mice display augmented neutrophil-mediated innate immunity
journal contribution
posted on 2023-05-18, 12:47 authored by Zhu, G, Augustine, MM, Azuma, T, Luo, L, Yao, S, Anand, S, Rietz, AC, Huang, J, Xu, H, Andrew FliesAndrew Flies, Tamada, K, Colonna, M, van Duersen, JMA, Chen, LB7-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.
History
Publication title
BloodVolume
113Issue
8Pagination
1759-1767ISSN
0006-4971Department/School
Menzies Institute for Medical ResearchPublisher
American Society of HematologyPlace of publication
United StatesRights statement
Copyright 2009 The American Society of HematologyRepository Status
- Restricted