1. Liver-resident NK cells suppress autoimmune cholangitis and limit the proliferation of CD4 + T cells.
- Author
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Zhao ZB, Lu FT, Ma HD, Wang YH, Yang W, Long J, Miao Q, Zhang W, Tian Z, Ridgway WM, Cao J, Gershwin ME, and Lian ZX
- Subjects
- Adoptive Transfer methods, Animals, Autoimmune Diseases blood, B-Lymphocytes immunology, Basic-Leucine Zipper Transcription Factors deficiency, Basic-Leucine Zipper Transcription Factors genetics, CD8-Positive T-Lymphocytes immunology, Cytokines blood, Disease Models, Animal, Disease Progression, Female, Hybridomas, Liver Cirrhosis, Biliary blood, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Receptor, Transforming Growth Factor-beta Type II genetics, Autoimmune Diseases complications, Autoimmune Diseases immunology, CD4-Positive T-Lymphocytes immunology, Killer Cells, Natural immunology, Liver immunology, Liver Cirrhosis, Biliary complications, Liver Cirrhosis, Biliary immunology
- 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.- Published
- 2020
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