B7-H3 promotes pathogenesis of autoimmune disease and inflammation by regulating the activity of different T cell subsets

Liqun Luo, Gefeng Zhu, Haiying Xu, Sheng Yao, Gang Zhou, Yuwen Zhu, Koji Tamada, Lanqing Huang, Andrew D. Flies, Megan Broadwater, William Ruff, Jan M A Van Deursen, Ignacio Melero, Zhou Zhu, Lieping Chen

Research output: Contribution to journalArticle

Abstract

B7-H3 is a cell surface molecule in the immunoglobulin superfamily that is frequently upregulated in response to autoantigens and pathogens during host T cell immune responses. However, B7-H3's role in the differential regulation of T cell subsets remains largely unknown. Therefore, we constructed a new B7-H3 deficient mouse strain (B7-H3 KO) and evaluated the functions of B7-H3 in the regulation of Th1, Th2, and Th17 subsets in experimental autoimmune encephalomyelitis (EAE), experimental asthma, and collagen-induced arthritis (CIA); these mouse models were used to predict human immune responses in multiple sclerosis, asthma, and rheumatoid arthritis, respectively. Here, we demonstrate that B7-H3 KO mice have significantly less inflammation, decreased pathogenesis, and limited disease progression in both EAE and CIA mouse models when compared with littermates; these results were accompanied by a decrease in IFN-γ and IL-17 production. In sharp contrast, B7-H3 KO mice developed severe ovalbumin (OVA)-induced asthma with characteristic infiltrations of eosinophils in the lung, increased IL-5 and IL-13 in lavage fluid, and elevated IgE anti-OVA antibodies in the blood. Our results suggest B7-H3 has a costimulatory function on Th1/Th17 but a coinhibitory function on Th2 responses. Our studies reveal that B7-H3 could affect different T cell subsets which have important implications for regulating pathogenesis and disease progression in human autoimmune disease.

Original languageEnglish (US)
Article numbere0130126
JournalPLoS One
Volume10
Issue number6
DOIs
StatePublished - Jun 11 2015

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ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Luo, L., Zhu, G., Xu, H., Yao, S., Zhou, G., Zhu, Y., Tamada, K., Huang, L., Flies, A. D., Broadwater, M., Ruff, W., Van Deursen, J. M. A., Melero, I., Zhu, Z., & Chen, L. (2015). B7-H3 promotes pathogenesis of autoimmune disease and inflammation by regulating the activity of different T cell subsets. PLoS One, 10(6), [e0130126]. https://doi.org/10.1371/journal.pone.0130126