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

Gefeng Zhu, Mathew M. Augustine, Takeshi Azuma, Liqun Luo, Sheng Yao, Sudarshan Anand, A. Cecilia Rietz, Jiaqiang Huang, Haiying Xu, Andrew S. Flies, Sarah J. Flies, Koji Tamada, Marco Colonna, Jan M A Van Deursen, Lieping Chen

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62 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1759-1767
Number of pages9
JournalBlood
Volume113
Issue number8
DOIs
StatePublished - Feb 19 2009

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Zhu, G., Augustine, M. M., Azuma, T., Luo, L., Yao, S., Anand, S., Rietz, A. C., Huang, J., Xu, H., Flies, A. S., Flies, S. J., Tamada, K., Colonna, M., Van Deursen, J. M. A., & Chen, L. (2009). B7-H4-deficient mice display augmented neutrophil-mediated innate immunity. Blood, 113(8), 1759-1767. https://doi.org/10.1182/blood-2008-01-133223