Your browser doesn't support javascript.
loading
A comparative study on roles of natural killer T cells in two diet-induced non-alcoholic steatohepatitis-related fibrosis in mice.
Zheng, Shumei; Yang, Wenzhuo; Yao, Dongmei; Tang, Shanhong; Hou, Juanni; Chang, Xing.
Afiliación
  • Zheng S; Department of Gastroenterology and Hepatology, The General Hospital of Western Theater Command, Chengdu, China.
  • Yang W; Department of Gastroenterology and Hepatology, Shanghai Tongji Hospital, Shanghai Tongji University, Shanghai, China.
  • Yao D; Department of Gastroenterology and Hepatology, the Second Hospital of Hebei Medical University, Shijiazhuang, China.
  • Tang S; Department of Gastroenterology and Hepatology, The General Hospital of Western Theater Command, Chengdu, China.
  • Hou J; Department of Gastroenterology and Hepatology, The General Hospital of Western Theater Command, Chengdu, China.
  • Chang X; Department of Gastroenterology and Hepatology, The General Hospital of Western Theater Command, Chengdu, China.
Ann Med ; 54(1): 2233-2245, 2022 12.
Article en En | MEDLINE | ID: mdl-35950602
BACKGROUND: Immune responses are important in the progression of non-alcoholic fatty liver disease (NAFLD). Natural killer T (NKT) cells are main components of the innate immune system that modulate immunity. However, the role of NKT cells in NAFLD remains controversial. OBJECTIVE: We aimed to investigate the role of NKT cells in non-alcoholic steatohepatitis (NASH)-related fibrosis in fast food diet (FFD)- and methionine choline-deficient (MCD) diet-induced mouse models. METHODS: Hepatic NKT cells were analysed in wild-type (WT) and CD1d-/- mice fed FFD or MCD diets. Hepatic pathology, cytokine profiles and liver fibrosis were evaluated. Furthermore, the effect of chronic administration of α-galactosylceramide (α-GalCer) on liver fibrosis was investigated in both FFD- and MCD-treated mice. RESULTS: FFD induced a significant depletion of hepatic NKT cells, thus leading to mild to moderate NASH and early-stage fibrosis, while mice fed MCD diets developed severe liver inflammation and progressive fibrosis without a significant change in hepatic NKT cell abundance. FFD induced a similar liver fibrogenic response in CD1d-/- and WT mice, while MCD induced a higher hepatic mRNA expression of Col1α1 and TIMP1 as well as relative fibrosis density in CD1d-/- mice than WT mice (31.8 vs. 16.3, p = .039; 40.0 vs. 22.6, p = .019; 2.24 vs. 1.59, p = .036). Chronic administration of α-GalCer induced a higher hepatic mRNA expression of TIMP1 in MCD-treated mice than controls (36.7 vs. 14.9, p = .005). CONCLUSION: NKT cells have protective roles in NAFLD as the disease progresses. During diet-induced steatosis, mild to moderate NASH and the early stage of fibrosis, hepatic NKT cells are relatively depleted, leading to a proinflammatory status. In severe NASH and the advanced stage of liver fibrosis, NKT cells play a role in inhibiting the NASH-related fibrogenic response. Chronic administration of α-GalCer induces NKT cell anergy and tolerance, which may play a role in promoting the liver fibrogenic response.
Asunto(s)
Palabras clave

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células T Asesinas Naturales / Enfermedad del Hígado Graso no Alcohólico Tipo de estudio: Etiology_studies Límite: Animals / Humans Idioma: En Revista: Ann Med Asunto de la revista: MEDICINA Año: 2022 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células T Asesinas Naturales / Enfermedad del Hígado Graso no Alcohólico Tipo de estudio: Etiology_studies Límite: Animals / Humans Idioma: En Revista: Ann Med Asunto de la revista: MEDICINA Año: 2022 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido