First Author | Bhattacharjee J | Year | 2017 |
Journal | Hepatol Commun | Volume | 1 |
Issue | 4 | Pages | 299-310 |
PubMed ID | 29152605 | Mgi Jnum | J:329818 |
Mgi Id | MGI:7344162 | Doi | 10.1002/hep4.1041 |
Citation | Bhattacharjee J, et al. (2017) Hepatic Natural Killer T-cell and CD8+ T-cell Signatures in Mice with Nonalcoholic Steatohepatitis. Hepatol Commun 1(4):299-310 |
abstractText | Hepatic inflammation is a key pathological feature of Nonalcoholic Steatohepatitis (NASH). Natural Killer T-cells (NKT) and CD8+ 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. Further, to better understand the impact of these cell populations; CD1d-deficient and CD8+ T-cell depleted mice were subjected to HFHC diet for 16 weeks. C57Bl6/J mice fed HFHC diet had increased body weight, liver triglyceride content, serum alanine aminotransferase (ALT) levels and increased NKT cells and CD8+ T-cells 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 HFHC had lower hepatic triglyceride content, lower ALT levels, as well reduced alpha-smooth muscle actin (alphaSMA), collagen type 1 alpha 1 (Col1a1), collagen type 1 alpha 2 (Col1a2) mRNA expression, lower activated resident macrophages and infiltrating macrophages and improved NAFLD activity scores. 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. |