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

Citation

Luo, L and Zhu, G and Xu, H and Yao, S and Zhou, G and Zhu, Y and Tamada, K and Huang, L and Flies, AS and Broadwater, M and Ruff, W and van Deursen, JMA and Melero, I and Zhu, Z and Chen, L, B7-H3 promotes pathogenesis of autoimmune disease and inflammation by regulating the activity of different T cell subsets, PLoS One, 10, (6) Article e0130126. ISSN 1932-6203 (2015) [Refereed Article]


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Copyright 2015 Luo et al Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) http://creativecommons.org/licenses/by/4.0/

DOI: doi:10.1371/journal.pone.0130126

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.

Item Details

Item Type:Refereed Article
Keywords:B7-H3
Research Division:Medical and Health Sciences
Research Group:Immunology
Research Field:Cellular Immunology
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Immune System and Allergy
Author:Flies, AS (Dr Andy Flies)
ID Code:102804
Year Published:2015
Web of Science® Times Cited:10
Deposited By:Menzies Institute for Medical Research
Deposited On:2015-09-07
Last Modified:2017-11-07
Downloads:223 View Download Statistics

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