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

• Published in: PloS one Vol. 10; no. 6; p. e0130126
• Main Authors: Luo, Liqun, Zhu, Gefeng, Xu, Haiying, Yao, Sheng, Zhou, Gang, Zhu, Yuwen, Tamada, Koji, Huang, Lanqing, Flies, Andrew D, Broadwater, Megan, Ruff, William, van Deursen, Jan M A, Melero, Ignacio, Zhu, Zhou, Chen, Lieping
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 11.06.2015; Public Library of Science (PLoS)
• Subjects: Analysis; Animal models; Animals; Antibodies; Apoptosis; Arthritis; Arthritis, Experimental - chemically induced; Arthritis, Experimental - immunology; Arthritis, Experimental - pathology; Asthma; Asthma - chemically induced; Asthma - immunology; Asthma - pathology; Autoantigens; Autoimmunity; B7 antigen; B7 Antigens - physiology; Blotting, Western; Cell Differentiation; Cell Proliferation; Cell surface; Cells, Cultured; Collagen; Development and progression; Disease control; Encephalomyelitis, Autoimmune, Experimental - chemically induced; Encephalomyelitis, Autoimmune, Experimental - immunology; Encephalomyelitis, Autoimmune, Experimental - pathology; Eosinophils; Experimental allergic encephalomyelitis; Female; Helper cells; Human behavior; Humans; Immune response; Immune response (cell-mediated); Immunoenzyme Techniques; Immunoglobulin E; Inflammation; Inflammation - chemically induced; Inflammation - immunology; Inflammation - pathology; Interleukin 13; Interleukin 17; Interleukin 5; Leukocytes (eosinophilic); Lungs; Lymphocyte Activation; Lymphocytes T; Mice; Mice, Inbred C57BL; Mice, Knockout; Molecular chains; Multiple sclerosis; Ovalbumin; Pathogenesis; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; Rheumatoid arthritis; Rheumatoid factor; RNA, Messenger - genetics; T cells; Th1 Cells - immunology; Th17 Cells - immunology; Th2 Cells - immunology; γ-Interferon; United States > US; Maryland; Baltimore Maryland; Connecticut
• DOI: 10.1371/journal.pone.0130126
• ISSN: 1932-6203

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.