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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| Format: | Article |
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Frontiers Media S.A.
2022-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.814155/full |
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| author | Rossella Fasano Rossella Fasano Eleonora Malerba Marcella Prete Antonio Giovanni Solimando Antonio Giovanni Solimando Alessio Buonavoglia Nicola Silvestris Nicola Silvestris Patrizia Leone Vito Racanelli |
| author_facet | Rossella Fasano Rossella Fasano Eleonora Malerba Marcella Prete Antonio Giovanni Solimando Antonio Giovanni Solimando Alessio Buonavoglia Nicola Silvestris Nicola Silvestris Patrizia Leone Vito Racanelli |
| author_sort | Rossella Fasano |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-24T01:45:25Z |
| format | Article |
| id | doaj.art-99481d11478a4ec9a90ee8f2602fdf41 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-24T01:45:25Z |
| publishDate | 2022-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-99481d11478a4ec9a90ee8f2602fdf412022-12-21T17:21:53ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-01-011210.3389/fimmu.2021.814155814155Impact of Antigen Presentation Mechanisms on Immune Response in Autoimmune HepatitisRossella Fasano0Rossella Fasano1Eleonora Malerba2Marcella Prete3Antonio Giovanni Solimando4Antonio Giovanni Solimando5Alessio Buonavoglia6Nicola Silvestris7Nicola Silvestris8Patrizia Leone9Vito Racanelli10Department of Biomedical Sciences and Human Oncology, “Aldo Moro” University of Bari Medical School, Bari, ItalyMedical Oncology Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Tumori Giovanni Paolo II, Bari, ItalyDepartment of Biomedical Sciences and Human Oncology, “Aldo Moro” University of Bari Medical School, Bari, ItalyDepartment of Biomedical Sciences and Human Oncology, “Aldo Moro” University of Bari Medical School, Bari, ItalyDepartment of Biomedical Sciences and Human Oncology, “Aldo Moro” University of Bari Medical School, Bari, ItalyMedical Oncology Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Tumori Giovanni Paolo II, Bari, ItalyDepartment of Biomedical Sciences and Human Oncology, “Aldo Moro” University of Bari Medical School, Bari, ItalyDepartment of Biomedical Sciences and Human Oncology, “Aldo Moro” University of Bari Medical School, Bari, ItalyMedical Oncology Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Tumori Giovanni Paolo II, Bari, ItalyDepartment of Biomedical Sciences and Human Oncology, “Aldo Moro” University of Bari Medical School, Bari, ItalyDepartment of Biomedical Sciences and Human Oncology, “Aldo Moro” University of Bari Medical School, Bari, ItalyThe 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.https://www.frontiersin.org/articles/10.3389/fimmu.2021.814155/fullautoimmune hepatitismajor histocompatibility complex class IImajor histocompatibility complex class Iantigen processing and presentationliver |
| spellingShingle | Rossella Fasano Rossella Fasano Eleonora Malerba Marcella Prete Antonio Giovanni Solimando Antonio Giovanni Solimando Alessio Buonavoglia Nicola Silvestris Nicola Silvestris Patrizia Leone Vito Racanelli Impact of Antigen Presentation Mechanisms on Immune Response in Autoimmune Hepatitis Frontiers in Immunology autoimmune hepatitis major histocompatibility complex class II major histocompatibility complex class I antigen processing and presentation liver |
| 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 | autoimmune hepatitis major histocompatibility complex class II major histocompatibility complex class I antigen processing and presentation liver |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.814155/full |
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