Biochemical and biophysical research communications · 2023
The transcription factor T-bet promotes the pathogenesis of nonalcoholic fatty liver disease by upregulating intrahepatic inflammation.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Sun Guangyong, Wei Yunxiong, Zhu Jingjing, Zheng Shimeng, Zhang Zihan, Zhang Dong
Аннотация
OBJECTIVE: To investigate the effect of the transcription factor T-bet on the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and the regulation of the intrahepatic immune microenvironment.
METHODS: Wild-type and T-bet knockout NASH mouse models were constructed. The effect of T-bet knockout on the pathogenesis of NAFLD was observed by histochemical staining. The expression of T-bet in immune cells in the liver and the effect of T-bet knockout on the proportion and function of immune cell subsets in the liver were determined by flow analysis.
RESULTS: Flow cytometry results indicated that T-bet expression was increased in immune cells, especially NKT cells, in the livers of NAFLD mice. Knocking out the transcription factor T-bet reduced intrahepatic inflammation, reduced lipid accumulation, and ameliorated the pathogenesis of NAFLD. Based on the analysis of immune cell subsets, knocking out the transcription factor T-bet decreased the proportion, survival, and degree of activation of NK, NKT, and CD8 T cells in NAFLD liver; additionally, it decreased the secretion of IFN-γ by T cells and NKT cells but had no effect on the proportion of Th17 cells and Treg cells. Knocking out the transcription factor T-bet also reduced the proportion of proinflammatory myeloid-derived macrophages (MoMFs) in NAFLD liver, mainly the proportion of proinflammatory Ly6Chigh MoMFs. Furthermore, knocking out the transcription factor T-bet had no significant effect on the secretion of TNF-α from MoMFs but significantly reduced the expression of MHC class II molecules. Further analysis showed that the transcription factor T-bet may directly affect the expression of MHC class II molecules H2-AB1 and H2-Dmb1 through transcriptional regulation.
CONCLUSIONS: Knocking out the transcription factor T-bet reduced the proinflammatory effect of innate immune cells (MoMFs, NK cells, and NKT cells) and T lymphocytes in NAFLD liver, thereby reducing intrahepatic inflammation and delaying the pathogenesis of NAFLD.
METHODS: Wild-type and T-bet knockout NASH mouse models were constructed. The effect of T-bet knockout on the pathogenesis of NAFLD was observed by histochemical staining. The expression of T-bet in immune cells in the liver and the effect of T-bet knockout on the proportion and function of immune cell subsets in the liver were determined by flow analysis.
RESULTS: Flow cytometry results indicated that T-bet expression was increased in immune cells, especially NKT cells, in the livers of NAFLD mice. Knocking out the transcription factor T-bet reduced intrahepatic inflammation, reduced lipid accumulation, and ameliorated the pathogenesis of NAFLD. Based on the analysis of immune cell subsets, knocking out the transcription factor T-bet decreased the proportion, survival, and degree of activation of NK, NKT, and CD8 T cells in NAFLD liver; additionally, it decreased the secretion of IFN-γ by T cells and NKT cells but had no effect on the proportion of Th17 cells and Treg cells. Knocking out the transcription factor T-bet also reduced the proportion of proinflammatory myeloid-derived macrophages (MoMFs) in NAFLD liver, mainly the proportion of proinflammatory Ly6Chigh MoMFs. Furthermore, knocking out the transcription factor T-bet had no significant effect on the secretion of TNF-α from MoMFs but significantly reduced the expression of MHC class II molecules. Further analysis showed that the transcription factor T-bet may directly affect the expression of MHC class II molecules H2-AB1 and H2-Dmb1 through transcriptional regulation.
CONCLUSIONS: Knocking out the transcription factor T-bet reduced the proinflammatory effect of innate immune cells (MoMFs, NK cells, and NKT cells) and T lymphocytes in NAFLD liver, thereby reducing intrahepatic inflammation and delaying the pathogenesis of NAFLD.