![]() ![]() Most normal healthy cells express MHC I receptors which mark these cells as ‘self’. Inhibitory receptors act as a check on NK cell killing. Activating receptors recognise molecules that are expressed on the surface of cancer cells and infectedĬells, and ‘switch on’ the NK cell. Whether or not the NK cell kills these cells depends on a balance of signals from activating receptors and inhibitory receptors on the NK cell surface. While on patrol NK cells constantly contact other cells. Additionally, NK cells secrete cytokines such as IFNγ and TNFα, which act on other immune cells like Macrophage and Dendritic cells to enhance the immune response. They are named for this ‘natural’ killing. NK cells were first noticed for their ability to kill tumour cells without any priming or prior activation (in contrast to cytotoxic T cells, which need priming by antigen presenting cells). As well as protecting against disease, specialized NK cells are also found in the placenta and may play an important role in pregnancy. NK cells are best known for killing virally infected cells, and detecting and controlling early signs of cancer. However, as cells of the innate immune system, NK cells are classified as group I Innate Lymphocytes (ILCs) and respond quickly to a wide variety of pathological challenges. **** P < 0.0001, * P < 0.05.Natural Killer (NK) Cells are lymphocytes in the same family as T and B cells, coming from a common progenitor. Statistical comparison was done using one‐way analysis of variance with Bonferroni correction for C,D. (D) Higher percentage of activated CD8 T‐cells in the livers of HFHC wild‐type mice compared to Chow wild‐type, Chow CD1dKO, and HFHC CD1dKO mice. (C) Graphical depiction of NAS among the chow/HFHC‐fed wild‐type and CD1dKO mice. Liver tissue of HFHC‐fed wild‐type mice showed deposition of collagen (black arrows). (B) Masson's trichrome staining images (magnification ×200 and ×400) of liver tissue of chow/HFHC‐fed wild‐type and CD1dKO mice. Liver tissue of the HFHC‐fed wild‐type mice shows vacuolated hepatocytes (red arrow). (A) Hematoxylin and eosin‐stained images (magnification ×400) of liver tissue of chow/HFHC‐fed wild‐type and CD1dKO mice. Histology of liver tissue, Masson's trichrome staining of liver tissue, and percentage abundance of activated CD8 T‐cells in the liver tissue for chow/HFHC‐fed CD1dKO and wild‐type mice. Depletion of these cells resulted in reduced NASH progression and thus presents novel therapeutic avenues for the treatment of NASH.įibrosis Inflammation Liver Obesity Steatosis. We found that NASH has an immunological signature that includes hepatic infiltrating NKT and CD8+ T-Cells. 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. In comparison, CD1d-deficient and CD8-T cell depleted mice fed HFHC had lower hepatic triglyceride content, lower ALT levels, as well reduced α-smooth muscle actin ( αSMA), 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. In addition human liver sections from patients with NASH showed increased CD8+ T-cells. 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. 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. 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. We hypothesized that these same inflammatory phenotypes would be present in progressive NASH. Natural Killer T-cells (NKT) and CD8+ T-cells are known to play an important role in obesity related adipose tissue inflammation. Hepatic inflammation is a key pathological feature of Nonalcoholic Steatohepatitis (NASH). ![]()
0 Comments
Leave a Reply. |
Details
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |