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Adoptive Induced Antigen-Specific Treg Cells Reverse Inflammation in Collagen-Induced Arthritis Mouse Model

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Abstract

Rheumatoid arthritis (RA) is a systemic autoimmune disease that may cause bone damage and worsening disability. Manipulating antigen-specific Treg cells is a promising approach to treat autoimmune disease since the immune suppressive function of Treg cells has the feature of antigen specificity which could avoid overall immune suppression. It has been known that the function of Treg cells is impaired in RA, and adoptive transfer of Treg cells is effective in suppressing RA. Here, we designed a new approach to generate antigen-specific Treg cells by culturing CD4+ T cells from mice with RA onset, and we also proved that the adoptive transfer of these antigen-specific Treg cells reversed the collagen-induced arthritis (CIA) progression by suppressing the key inflammatory cytokine TNF-α. Further analysis showed that the transferred Treg cells were stable in vivo. These findings suggest this novel approach may have clinical applications for treatment of autoimmunity, including RA and other autoimmune disorders.

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Funding

This work was supported by grants from the National Natural Science Foundations of China (NO.81600876), the Promotive Research Fund for Excellent Young and Middle-Aged Scientists of Shandong Province (BS2010YY054), the Science Foundation for The Youth Scholars of Sichuan University (NO.2016SCU11048), Shandong Medical and Health Technology Development (2014WSB04020), Shandong Provincial Natural Science Foundation (ZR2015HM060), and Shandong Provincial Science and Technology Development Projects Foundation (2013GSF31805).

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Authors and Affiliations

  1. Department of Orthopaedics, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, China

    Guangzhi Sun & Xinfeng Yan

  2. Department of Rheumatology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, China

    Yanfeng Hou

  3. State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases and Department of Oral Medicine of West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China

    Wang Gong, Sai Liu, Yao Yuan, Dunfang Zhang & Qianming Chen

  4. Viral Oncology Program, Center for Cancer and Metabolism, SRI International, Menlo Park, CA, USA

    Jia Li

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  1. Guangzhi Sun
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  2. Yanfeng Hou
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  3. Wang Gong
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  4. Sai Liu
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  7. Dunfang Zhang
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  9. Xinfeng Yan
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Corresponding authors

Correspondence to Dunfang Zhang or Xinfeng Yan.

Ethics declarations

All animal studies were approved by the Subcommittee on Research and Animal Care (SRAC) of Shandong University and Sichuan University, and were performed by following the guidelines of Experimental Animal Center of Shandong University and Sichuan University for the use and care of live animals.

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The authors declare that there is no conflict of interest.

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Sun, G., Hou, Y., Gong, W. et al. Adoptive Induced Antigen-Specific Treg Cells Reverse Inflammation in Collagen-Induced Arthritis Mouse Model. Inflammation 41, 485–495 (2018). https://doi.org/10.1007/s10753-017-0704-4

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  • DOI: https://doi.org/10.1007/s10753-017-0704-4

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