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

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 dnTGF beta RII 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 dnTGF beta RII 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.