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

Zhi Bin Zhao, Fang Ting Lu, Hong Di Ma, Yin Hu Wang, Wei Yang, Jie Long, Qi Miao, Weici Zhang, Zhigang Tian, William M. Ridgway, Jie Cao, M. Eric Gershwin, Zhe Xiong Lian

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3 Scopus citations

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 CD11c hi 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.

Original languageEnglish (US)
JournalCellular and Molecular Immunology
DOIs
StatePublished - Jan 1 2019

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Keywords

  • CD4 T cell
  • Cholangitis
  • Liver-resident NK
  • Suppression

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Zhao, Z. B., Lu, F. T., Ma, H. D., Wang, Y. H., Yang, W., Long, J., Miao, Q., Zhang, W., Tian, Z., Ridgway, W. M., Cao, J., Gershwin, M. E., & Lian, Z. X. (2019). Liver-resident NK cells suppress autoimmune cholangitis and limit the proliferation of CD4 + T cells Cellular and Molecular Immunology. https://doi.org/10.1038/s41423-019-0199-z