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Proteomic analysis reveals distinctive protein profiles involved in CD8+ T cell-mediated murine autoimmune cholangitis

Cellular & Molecular Immunology volume 15, pages 756–767 (2018)Cite this article

Abstract

Autoimmune cholangitis arises from abnormal innate and adaptive immune responses in the liver, and T cells are critical drivers in this process. However, little is known about the regulation of their functional behavior during disease development. We previously reported that mice with T cell-restricted expression of a dominant negative form of transforming growth factor beta receptor type II (dnTGFβRII) spontaneously develop an autoimmune cholangitis that resembles human primary biliary cholangitis (PBC). Adoptive transfer of CD8+ but not CD4+ T cells into Rag1−/− mice reproduced the disease, demonstrating a critical role for CD8+ T cells in PBC pathogenesis. Herein, we used SOMAscan technology to perform proteomic analysis of serum samples from dnTGFβRII and B6 control mice at different ages. In addition, we analyzed CD8 protein profiles after adoptive transfer of splenic CD8+ cells into Rag1−/− recipients. The use of the unique SOMAscan aptamer technology revealed critical and distinct profiles of CD8 cells, which are key to biliary mediation. In total, 254 proteins were significantly increased while 216 proteins were significantly decreased in recipient hepatic CD8+ cells compared to donor splenic CD8+ cells. In contrast to donor splenic CD8+ cells, recipient hepatic CD8+ cells expressed distinct profiles for proteins involved in chemokine signaling, focal adhesion, T cell receptor and natural killer cell-mediated cytotoxicity pathways.

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Acknowledgements

Financial Support: Funded by National Institutes of Health grant DK090019.

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Author notes

  1. Co-first author.

  2. Current address: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Authors and Affiliations

  1. Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, USA, California

    Weici Zhang, Ren Zhang, Jun Zhang, Ying Sun, Patrick SC Leung, Guo-Xiang Yang, Zongwen Shuai & M Eric Gershwin

  2. Department of Pathogenic Biology and Immunology, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China

    Ren Zhang

  3. Center for non-infectious liver diseases, Beijing 302 Hospital, Beijing, 100039, China

    Ying Sun

  4. Department of Rheumatology and Immunology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China

    Zongwen Shuai

  5. Division of Immunology, Allergy and Rheumatology, University of Cincinnati, Cincinnati, 45267, OH, USA

    William M Ridgway

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Zhang, W., Zhang, R., Zhang, J. et al. Proteomic analysis reveals distinctive protein profiles involved in CD8+ T cell-mediated murine autoimmune cholangitis. Cell Mol Immunol 15, 756–767 (2018). https://doi.org/10.1038/cmi.2017.149

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