Liver-resident NK cells suppress autoimmune cholangitis and limit the proliferation of CD4+ T cells. Academic Article uri icon

Overview

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.

publication date

  • March 15, 2019

Research

keywords

  • Autoimmune Diseases
  • CD4-Positive T-Lymphocytes
  • Killer Cells, Natural
  • Liver
  • Liver Cirrhosis, Biliary

Identity

PubMed Central ID

  • PMC7000693

Scopus Document Identifier

  • 85062952065

Digital Object Identifier (DOI)

  • 10.1084/jem.20181076

PubMed ID

  • 30874628

Additional Document Info

volume

  • 17

issue

  • 2