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Liver-resident NK cells suppress autoimmune cholangitis and limit the proliferation of CD4+ T cells

Cellular & Molecular Immunology volume 17, pages 178–189 (2020)Cite this article

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Abstract

Liver-resident NK cells are distinct from conventional NK cells and play an important role in the maintenance of liver homeostasis. How liver-resident NK cells participate in autoimmune cholangitis remains unclear. Here, we extensively investigated the impact of NK cells in the pathogenesis of autoimmune cholangitis utilizing the well-established dnTGFβRII cholangitis model, NK cell-deficient (Nfil3−/−) mice, adoptive transfer and in vivo antibody-mediated NK cell depletion. Our data demonstrated that disease progression was associated with a significantly reduced frequency of hepatic NK cells. Depletion of NK cells resulted in exacerbated autoimmune cholangitis in dnTGFβRII mice. We further confirmed that the DX5−CD11chi liver-resident NK cell subset colocalized with CD4+ T cells and inhibited CD4+ T cell proliferation. Gene expression microarray analysis demonstrated that liver-resident NK cells had a distinct gene expression pattern consisting of the increased expression of genes involved in negative regulatory functions in the context of the inflammatory microenvironment.

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Acknowledgements

This study was supported by the Program for Guangdong Introducing Innovative and Entrepreneurial Teams (2017ZT07S054), the National Natural Science Foundation of China (81601416, 81430034, 91542123), the National Key R&D Program of China (2017YFA0205600) and a National Institutes of Health grant (DK090019).

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Author notes

  1. These authors contributed equally: Zhi-Bin Zhao, Fang-Ting Lu, Hong-Di Ma.

Authors and Affiliations

  1. Department of General Surgery, Guangzhou Digestive Disease Center, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510180, China

    Zhi-Bin Zhao, Jie Long, Jie Cao & Zhe-Xiong Lian

  2. Chronic Disease Laboratory, Institutes for Life Sciences and School of Medicine, South China University of Technology, Guangzhou, 510006, China

    Zhi-Bin Zhao, Jie Long & Zhe-Xiong Lian

  3. Institute of Immunology and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, 230027, China

    Zhi-Bin Zhao, Hong-Di Ma, Yin-Hu Wang, Wei Yang, Jie Long, Zhigang Tian & Zhe-Xiong Lian

  4. Center for Reproductive Medicine, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei, Anhui, China

    Fang-Ting Lu

  5. Department of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

    Qi Miao

  6. Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis School of Medicine, Davis, CA, USA

    Weici Zhang & M. Eric Gershwin

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

    William M. Ridgway

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Correspondence to Jie Cao, M. Eric Gershwin or Zhe-Xiong Lian.

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Zhao, ZB., Lu, FT., Ma, HD. et al. Liver-resident NK cells suppress autoimmune cholangitis and limit the proliferation of CD4+ T cells. Cell Mol Immunol 17, 178–189 (2020). https://doi.org/10.1038/s41423-019-0199-z

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