Title

Hepatic Natural Killer T-Cell And Cd8+ T-Cell Signatures In Mice With Nonalcoholic Steatohepatitis

Abstract

Hepatic inflammation is a key pathologic feature of nonalcoholic steatohepatitis (NASH). Natural killer T (NKT) cells and clusters of differentiation (CD)8+ T-cells are known to play an important role in obesity-related adipose tissue inflammation. We hypothesized that these same inflammatory phenotypes would be present in progressive NASH. We used a previously established high-fat high-carbohydrate (HFHC) murine obesogenic diet model of progressive NASH to investigate the role of NKT cells and CD8+ T-cells in C57Bl6/J mice. To better understand the impact of these cell populations, CD1d-deficient and CD8+ T-cell-depleted mice were subjected to an HFHC diet for 16 weeks. C57Bl6/J mice fed an HFHC diet had increased body weight, liver triglyceride content, serum alanine aminotransferase levels, and increased NKT-cell and CD8+ T-cell infiltration in the liver. In addition, human liver sections from patients with NASH showed increased CD8+ T-cells. In comparison, CD1d-deficient and CD8 T-cell-depleted mice fed an HFHC diet had a lower hepatic triglyceride content, lower alanine aminotransferase levels, lower activated resident macrophages and infiltrating macrophages, improved nonalcoholic fatty liver disease activity scores, and reduced α-smooth muscle actin, collagen type 1 alpha 1, and collagen type 1 alpha 2 messenger RNA expression. Further, while CD1d-deficient mice were protected against weight gain on the HFHC diet, CD8 T-cell-depleted mice gained weight on the HFHC diet. Conclusion: We found that NASH has an immunological signature that includes hepatic infiltrating NKT and CD8+ T-cells. Depletion of these cells resulted in reduced NASH progression and thus presents novel therapeutic avenues for the treatment of NASH. (Hepatology Communications 2017;1:299–310).

Publication Date

1-1-2017

Publication Title

Hepatology Communications

Volume

1

Issue

4

Number of Pages

299-310

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1002/hep4.1041

Socpus ID

85040009275 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/85040009275

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