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The role of osteopontin in the induction of the CD40 ligand in Graves' disease

Authors

  • Yicheng Qi,

    1. Shanghai Clinical Centre for Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolism, Ruijin Hospital, Affiliated to Shanghai Jiao-Tong University School of Medicine, Shanghai, China
    2. Laboratory of Endocrinology and Metabolism, Institute of Health Sciences, Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS) & Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, China
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  • Xiaoli Li,

    1. Shanghai Clinical Centre for Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolism, Ruijin Hospital, Affiliated to Shanghai Jiao-Tong University School of Medicine, Shanghai, China
    2. Laboratory of Endocrinology and Metabolism, Institute of Health Sciences, Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS) & Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, China
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  • Xinran Ma,

    1. Laboratory of Endocrinology and Metabolism, Institute of Health Sciences, Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS) & Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, China
    2. Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA
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  • Lingyan Xu,

    1. Laboratory of Endocrinology and Metabolism, Institute of Health Sciences, Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS) & Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, China
    2. Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA
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  • Xiaofang Zhang,

    1. Shanghai Clinical Centre for Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolism, Ruijin Hospital, Affiliated to Shanghai Jiao-Tong University School of Medicine, Shanghai, China
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  • Xiaohua Jiang,

    1. Shanghai Clinical Centre for Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolism, Ruijin Hospital, Affiliated to Shanghai Jiao-Tong University School of Medicine, Shanghai, China
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  • Jie Hong,

    1. Shanghai Clinical Centre for Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolism, Ruijin Hospital, Affiliated to Shanghai Jiao-Tong University School of Medicine, Shanghai, China
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  • Bin Cui,

    1. Shanghai Clinical Centre for Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolism, Ruijin Hospital, Affiliated to Shanghai Jiao-Tong University School of Medicine, Shanghai, China
    2. Laboratory of Endocrinology and Metabolism, Institute of Health Sciences, Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS) & Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, China
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  • Guang Ning,

    Corresponding author
    1. Shanghai Clinical Centre for Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolism, Ruijin Hospital, Affiliated to Shanghai Jiao-Tong University School of Medicine, Shanghai, China
    2. Laboratory of Endocrinology and Metabolism, Institute of Health Sciences, Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS) & Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, China
    • Correspondence: Guang Ning, Shu Wang, Shanghai Clinical Centre for Endocrine and Metabolic Diseases, and Department of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Affiliated to Shanghai Jiao-Tong University School of Medicine, 197 Rui-Jin 2nd Road, Shanghai 200025, China. Tel.: 86 21 64370045, Fax: 86 21 64333548; E-mails: guangning@medmail.com.cn; shuwang9999@163.com

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  • Shu Wang

    Corresponding author
    1. Shanghai Clinical Centre for Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolism, Ruijin Hospital, Affiliated to Shanghai Jiao-Tong University School of Medicine, Shanghai, China
    2. Laboratory of Endocrinology and Metabolism, Institute of Health Sciences, Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS) & Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, China
    • Correspondence: Guang Ning, Shu Wang, Shanghai Clinical Centre for Endocrine and Metabolic Diseases, and Department of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Affiliated to Shanghai Jiao-Tong University School of Medicine, 197 Rui-Jin 2nd Road, Shanghai 200025, China. Tel.: 86 21 64370045, Fax: 86 21 64333548; E-mails: guangning@medmail.com.cn; shuwang9999@163.com

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  • Yicheng Qi and Xiaoli Li contributed equally to this work.

Summary

Objective

Graves' disease (GD) is a common autoimmune disease involved autoantibody production. Although we previously reported that osteopontin (OPN), a proinflammatory protein, affected development of GD through NF-κB activation, little is known about the role of OPN in regulating immunoglobulin production in GD. CD40 Ligand (CD40L) is expressed on the surface of activated CD4+T cells and costimulates CD40 on B cells, stimulating production of immunoglobulins, a process which has been reported to play a vital role in immunological signalling transduction in several autoimmune diseases. This study sought to characterize the relationship between CD40L and GD development, as well as investigating the role of OPN in modulating immunoglobulin production in GD via CD40L.

Methods

Forty incident patients with GD, twenty-one patients with GD in remission and twenty-seven healthy controls were recruited. Both membrane-bound and soluble forms of CD40L were measured, and their correlations with clinical parameters were studied. In addition, correlation between OPN and CD40L level was also examined. Furthermore, we studied the regulatory effect of OPN on CD40L in CD4+T cells.

Results

We demonstrated that the CD40L levels were enhanced in patients with GD and recovered in patients with GD in remission. CD40L levels correlated with clinical GD diagnostic parameters and OPN concentration. Moreover, human recombinant OPN and plasma samples from patients with GD increased CD40L expression, which could be significantly suppressed by OPN monoclonal antibody. In addition, CD40L antibody blocked the immunoglobulin production augmented by OPN in cultured peripheral blood mononuclear cells (PBMCs), isolated from patients with GD and healthy subjects.

Conclusion

These results indicate that CD40L is induced by OPN and serves as the downstream effector of OPN for immunoglobulin production in GD development.

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