The immune response as a therapeutic target in non-alcoholic fatty liver disease
Non-alcoholic fatty liver disease (NAFLD) is a complex and heterogeneous disorder considered a liver-damaging manifestation of metabolic syndrome. Its prevalence has increased in the last decades due to modern-day lifestyle factors associated with overweight and obesity, making it a relevant public...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.954869/full |
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| author | Nicolás Ortiz-López Nicolás Ortiz-López Catalina Fuenzalida Catalina Fuenzalida María Soledad Dufeu María Soledad Dufeu Araceli Pinto-León Alejandro Escobar Jaime Poniachik Juan Pablo Roblero Lucía Valenzuela-Pérez Lucía Valenzuela-Pérez Caroll J. Beltrán Caroll J. Beltrán |
| author_facet | Nicolás Ortiz-López Nicolás Ortiz-López Catalina Fuenzalida Catalina Fuenzalida María Soledad Dufeu María Soledad Dufeu Araceli Pinto-León Alejandro Escobar Jaime Poniachik Juan Pablo Roblero Lucía Valenzuela-Pérez Lucía Valenzuela-Pérez Caroll J. Beltrán Caroll J. Beltrán |
| author_sort | Nicolás Ortiz-López |
| collection | DOAJ |
| description | Non-alcoholic fatty liver disease (NAFLD) is a complex and heterogeneous disorder considered a liver-damaging manifestation of metabolic syndrome. Its prevalence has increased in the last decades due to modern-day lifestyle factors associated with overweight and obesity, making it a relevant public health problem worldwide. The clinical progression of NAFLD is associated with advanced forms of liver injury such as fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). As such, diverse pharmacological strategies have been implemented over the last few years, principally focused on metabolic pathways involved in NAFLD progression. However, a variable response rate has been observed in NAFLD patients, which is explained by the interindividual heterogeneity of susceptibility to liver damage. In this scenario, it is necessary to search for different therapeutic approaches. It is worth noting that chronic low-grade inflammation constitutes a central mechanism in the pathogenesis and progression of NAFLD, associated with abnormal composition of the intestinal microbiota, increased lymphocyte activation in the intestine and immune effector mechanisms in liver. This review aims to discuss the current knowledge about the role of the immune response in NAFLD development. We have focused mainly on the impact of altered gut-liver-microbiota axis communication on immune cell activation in the intestinal mucosa and the role of subsequent lymphocyte homing to the liver in NAFLD development. We further discuss novel clinical trials that addressed the control of the liver and intestinal immune response to complement current NAFLD therapies. |
| first_indexed | 2024-04-12T13:43:35Z |
| format | Article |
| id | doaj.art-28cb28ec3926465ba58e302744073b19 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T13:43:35Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-28cb28ec3926465ba58e302744073b192022-12-22T03:30:46ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-10-011310.3389/fimmu.2022.954869954869The immune response as a therapeutic target in non-alcoholic fatty liver diseaseNicolás Ortiz-López0Nicolás Ortiz-López1Catalina Fuenzalida2Catalina Fuenzalida3María Soledad Dufeu4María Soledad Dufeu5Araceli Pinto-León6Alejandro Escobar7Jaime Poniachik8Juan Pablo Roblero9Lucía Valenzuela-Pérez10Lucía Valenzuela-Pérez11Caroll J. Beltrán12Caroll J. Beltrán13Laboratory of Immunogastroenterology, Unit of Gastroenterology, Department of Medicine, Hospital Clínico Universidad de Chile, Santiago, ChileSchool of Medicine, Faculty of Medicine, Universidad de Chile, Santiago, ChileLaboratory of Immunogastroenterology, Unit of Gastroenterology, Department of Medicine, Hospital Clínico Universidad de Chile, Santiago, ChileSchool of Medicine, Faculty of Medicine, Universidad de Chile, Santiago, ChileLaboratory of Immunogastroenterology, Unit of Gastroenterology, Department of Medicine, Hospital Clínico Universidad de Chile, Santiago, ChileSchool of Medicine, Faculty of Medicine, Universidad de Chile, Santiago, ChileLaboratory of Immunogastroenterology, Unit of Gastroenterology, Department of Medicine, Hospital Clínico Universidad de Chile, Santiago, ChileFaculty of Dentistry, Universidad de Chile, Santiago, ChileUnit of Gastroenterology, Department of Medicine, Hospital Clínico Universidad de Chile, Santiago, ChileUnit of Gastroenterology, Department of Medicine, Hospital Clínico Universidad de Chile, Santiago, ChileLaboratory of Immunogastroenterology, Unit of Gastroenterology, Department of Medicine, Hospital Clínico Universidad de Chile, Santiago, ChileSchool of Medicine, Faculty of Medicine, Universidad de Chile, Santiago, ChileLaboratory of Immunogastroenterology, Unit of Gastroenterology, Department of Medicine, Hospital Clínico Universidad de Chile, Santiago, ChileSchool of Medicine, Faculty of Medicine, Universidad de Chile, Santiago, ChileNon-alcoholic fatty liver disease (NAFLD) is a complex and heterogeneous disorder considered a liver-damaging manifestation of metabolic syndrome. Its prevalence has increased in the last decades due to modern-day lifestyle factors associated with overweight and obesity, making it a relevant public health problem worldwide. The clinical progression of NAFLD is associated with advanced forms of liver injury such as fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). As such, diverse pharmacological strategies have been implemented over the last few years, principally focused on metabolic pathways involved in NAFLD progression. However, a variable response rate has been observed in NAFLD patients, which is explained by the interindividual heterogeneity of susceptibility to liver damage. In this scenario, it is necessary to search for different therapeutic approaches. It is worth noting that chronic low-grade inflammation constitutes a central mechanism in the pathogenesis and progression of NAFLD, associated with abnormal composition of the intestinal microbiota, increased lymphocyte activation in the intestine and immune effector mechanisms in liver. This review aims to discuss the current knowledge about the role of the immune response in NAFLD development. We have focused mainly on the impact of altered gut-liver-microbiota axis communication on immune cell activation in the intestinal mucosa and the role of subsequent lymphocyte homing to the liver in NAFLD development. We further discuss novel clinical trials that addressed the control of the liver and intestinal immune response to complement current NAFLD therapies.https://www.frontiersin.org/articles/10.3389/fimmu.2022.954869/fullnon-alcoholic fatty liver disease (NAFLD)microbiota-gut-liver axislow-grade inflammationliver lymphocyte homingsteatohepatitis (NASH)microbiota |
| spellingShingle | Nicolás Ortiz-López Nicolás Ortiz-López Catalina Fuenzalida Catalina Fuenzalida María Soledad Dufeu María Soledad Dufeu Araceli Pinto-León Alejandro Escobar Jaime Poniachik Juan Pablo Roblero Lucía Valenzuela-Pérez Lucía Valenzuela-Pérez Caroll J. Beltrán Caroll J. Beltrán The immune response as a therapeutic target in non-alcoholic fatty liver disease Frontiers in Immunology non-alcoholic fatty liver disease (NAFLD) microbiota-gut-liver axis low-grade inflammation liver lymphocyte homing steatohepatitis (NASH) microbiota |
| title | The immune response as a therapeutic target in non-alcoholic fatty liver disease |
| title_full | The immune response as a therapeutic target in non-alcoholic fatty liver disease |
| title_fullStr | The immune response as a therapeutic target in non-alcoholic fatty liver disease |
| title_full_unstemmed | The immune response as a therapeutic target in non-alcoholic fatty liver disease |
| title_short | The immune response as a therapeutic target in non-alcoholic fatty liver disease |
| title_sort | immune response as a therapeutic target in non alcoholic fatty liver disease |
| topic | non-alcoholic fatty liver disease (NAFLD) microbiota-gut-liver axis low-grade inflammation liver lymphocyte homing steatohepatitis (NASH) microbiota |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.954869/full |
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