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Impact of Antigen Presentation Mechanisms on Immune Response in Autoimmune Hepatitis

The liver is a very tolerogenic organ. It is continually exposed to a multitude of antigens and is able to promote an effective immune response against pathogens and simultaneously immune tolerance against self-antigens. In spite of strong peripheral and central tolerogenic mechanisms, loss of toler...

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Autores principales: Fasano, Rossella, Malerba, Eleonora, Prete, Marcella, Solimando, Antonio Giovanni, Buonavoglia, Alessio, Silvestris, Nicola, Leone, Patrizia, Racanelli, Vito
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8804214/
https://www.ncbi.nlm.nih.gov/pubmed/35116039
http://dx.doi.org/10.3389/fimmu.2021.814155
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author Fasano, Rossella
Malerba, Eleonora
Prete, Marcella
Solimando, Antonio Giovanni
Buonavoglia, Alessio
Silvestris, Nicola
Leone, Patrizia
Racanelli, Vito
author_facet Fasano, Rossella
Malerba, Eleonora
Prete, Marcella
Solimando, Antonio Giovanni
Buonavoglia, Alessio
Silvestris, Nicola
Leone, Patrizia
Racanelli, Vito
author_sort Fasano, Rossella
collection PubMed
description The liver is a very tolerogenic organ. It is continually exposed to a multitude of antigens and is able to promote an effective immune response against pathogens and simultaneously immune tolerance against self-antigens. In spite of strong peripheral and central tolerogenic mechanisms, loss of tolerance can occur in autoimmune liver diseases, such as autoimmune hepatitis (AIH) through a combination of genetic predisposition, environmental factors, and an imbalance in immunological regulatory mechanisms. The liver hosts several types of conventional resident antigen presenting cells (APCs) such as dendritic cells, B cells and macrophages (Kupffer cells), and unconventional APCs including liver sinusoidal endothelial cells, hepatic stellate cells and hepatocytes. By standard (direct presentation and cross-presentation) and alternative mechanisms (cross-dressing and MHC class II-dressing), liver APCs presents self-antigen to naive T cells in the presence of costimulation leading to an altered immune response that results in liver injury and inflammation. Additionally, the transport of antigens and antigen:MHC complexes by trogocytosis and extracellular vesicles between different cells in the liver contributes to enhance antigen presentation and amplify autoimmune response. Here, we focus on the impact of antigen presentation on the immune response in the liver and on the functional role of the immune cells in the induction of liver inflammation. A better understanding of these key pathogenic aspects could facilitate the establishment of novel therapeutic strategies in AIH.
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spelling pubmed-88042142022-02-02 Impact of Antigen Presentation Mechanisms on Immune Response in Autoimmune Hepatitis Fasano, Rossella Malerba, Eleonora Prete, Marcella Solimando, Antonio Giovanni Buonavoglia, Alessio Silvestris, Nicola Leone, Patrizia Racanelli, Vito Front Immunol Immunology The liver is a very tolerogenic organ. It is continually exposed to a multitude of antigens and is able to promote an effective immune response against pathogens and simultaneously immune tolerance against self-antigens. In spite of strong peripheral and central tolerogenic mechanisms, loss of tolerance can occur in autoimmune liver diseases, such as autoimmune hepatitis (AIH) through a combination of genetic predisposition, environmental factors, and an imbalance in immunological regulatory mechanisms. The liver hosts several types of conventional resident antigen presenting cells (APCs) such as dendritic cells, B cells and macrophages (Kupffer cells), and unconventional APCs including liver sinusoidal endothelial cells, hepatic stellate cells and hepatocytes. By standard (direct presentation and cross-presentation) and alternative mechanisms (cross-dressing and MHC class II-dressing), liver APCs presents self-antigen to naive T cells in the presence of costimulation leading to an altered immune response that results in liver injury and inflammation. Additionally, the transport of antigens and antigen:MHC complexes by trogocytosis and extracellular vesicles between different cells in the liver contributes to enhance antigen presentation and amplify autoimmune response. Here, we focus on the impact of antigen presentation on the immune response in the liver and on the functional role of the immune cells in the induction of liver inflammation. A better understanding of these key pathogenic aspects could facilitate the establishment of novel therapeutic strategies in AIH. Frontiers Media S.A. 2022-01-18 /pmc/articles/PMC8804214/ /pubmed/35116039 http://dx.doi.org/10.3389/fimmu.2021.814155 Text en Copyright © 2022 Fasano, Malerba, Prete, Solimando, Buonavoglia, Silvestris, Leone and Racanelli https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Fasano, Rossella
Malerba, Eleonora
Prete, Marcella
Solimando, Antonio Giovanni
Buonavoglia, Alessio
Silvestris, Nicola
Leone, Patrizia
Racanelli, Vito
Impact of Antigen Presentation Mechanisms on Immune Response in Autoimmune Hepatitis
title Impact of Antigen Presentation Mechanisms on Immune Response in Autoimmune Hepatitis
title_full Impact of Antigen Presentation Mechanisms on Immune Response in Autoimmune Hepatitis
title_fullStr Impact of Antigen Presentation Mechanisms on Immune Response in Autoimmune Hepatitis
title_full_unstemmed Impact of Antigen Presentation Mechanisms on Immune Response in Autoimmune Hepatitis
title_short Impact of Antigen Presentation Mechanisms on Immune Response in Autoimmune Hepatitis
title_sort impact of antigen presentation mechanisms on immune response in autoimmune hepatitis
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8804214/
https://www.ncbi.nlm.nih.gov/pubmed/35116039
http://dx.doi.org/10.3389/fimmu.2021.814155
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