title: B7-H3 Promotes Pathogenesis of Autoimmune Disease and Inflammation by Regulating the Activity of Different T Cell Subsets.
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.
authors.affiliation: Institute of Immunotherapy, Sun Yat-Sen University, Guangzhou, Guangdong, China.
authors.forename: Liqun
authors.initials: L
authors.lastname: Luo
authors.affiliation: Department of Immunobiology and Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Gefeng
authors.initials: G
authors.lastname: Zhu
authors.affiliation: Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Haiying
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Immunobiology and Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Sheng
authors.initials: S
authors.lastname: Yao
authors.affiliation: Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Gang
authors.initials: G
authors.lastname: Zhou
authors.affiliation: Department of Immunobiology and Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Yuwen
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Koji
authors.initials: K
authors.lastname: Tamada
authors.affiliation: Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Lanqing
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Flies
authors.affiliation: Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Megan
authors.initials: M
authors.lastname: Broadwater
authors.affiliation: Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: William
authors.initials: W
authors.lastname: Ruff
authors.affiliation: Department of Pediatrics, Mayo Clinic, Rochester, Minnesota, United States of America.
authors.forename: Jan M A
authors.initials: JM
authors.lastname: van Deursen
authors.affiliation: Department of Medicine, University of Navarra, Pamplona, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Melero
authors.affiliation: Department of Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of Immunobiology and Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Lieping
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000276:immunology / Q000473:pathology*; D001249:Asthma / Q000139:chemically induced / Q000276:immunology / Q000473:pathology*; D060887:B7 Antigens / Q000502:physiology*; D015153:Blotting, Western; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000276:immunology / Q000473:pathology*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology / Q000473:pathology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D060887:B7 Antigens; C486038:Cd276 protein, mouse; D012333:RNA, Messenger