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PLoS One. 2015 Jun 11;10(6):e0130126. doi: 10.1371/journal.pone.0130126. eCollection 2015.

B7-H3 Promotes Pathogenesis of Autoimmune Disease and Inflammation by Regulating the Activity of Different T Cell Subsets.

Author information

1
Institute of Immunotherapy, Sun Yat-Sen University, Guangzhou, Guangdong, China.
2
Department of Immunobiology and Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America.
3
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
4
Department of Pediatrics, Mayo Clinic, Rochester, Minnesota, United States of America.
5
Department of Medicine, University of Navarra, Pamplona, Spain.
6
Department of Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America.

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.

PMID:
26065426
PMCID:
PMC4465912
DOI:
10.1371/journal.pone.0130126
[Indexed for MEDLINE]
Free PMC Article

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