The liver is a tolerogenic organ. Despite receiving both dietary and microbial antigens from its dual blood supply comprising arterial blood and blood from the gut via the portal vein, it maintains tolerance to these foreign antigens through its unique and powerful immune system, working in harmony to protect liver parenchyma cells and bile ducts. However, when this tolerogenic status breaks down, autoimmune liver diseases [autoimmune hepatitis (AIH)/autoimmune sclerosing cholangitis (ASC)/primary biliary cholangitis (PBC)] occur. The possible triggers leading to tolerance breakdown include certain viral infections and drugs. There are also certain predisposition HLA genes such as HLA DRB1*0301 (DR3), - 0701 (DR7), -1301 (DR13) and haplotype HLA A1-B8-DR3 in patients of Northern European ancestry and DR4 in Chinese and Japanese for AIH/ASC and HLA DRB1*0801 for PBC. Patients possessing these genes have more severe liver disease than those without. In addition, there is preliminary data showing that patients with AIH/ASC with the HLA-DR3/DR7/DR13 genes display Treg frequency lower than non-HLA-DR3/DR7/DR13 subjects. This could indicate that autoimmune disease predisposition HLA genes are associated with overt autoantigen presentation and hamper immunoregulation, leading to perpetuation of liver autoimmunity. However, the exact mechanisms played by HLA genes in liver specific autoimmunity remains unknown and needs to be explored.
This Research Topic aims to establish the links between HLA genes and clinical manifestations in a diverse population so that it is inclusive of different races and ethnicities. Secondly, the aim is to provide insight into how HLA genes impact autoantigen presentation, with a particular focus on autoantigen specific immunoregulation. This may allow tailoring of future therapeutic interventions to block overt antigen presentation and thereby establish more effective control of autoimmune disease. The ultimate goal is to restore the liver tolerogenic status by the development of novel therapeutic approaches, including peptide vaccines, in order to replace the current need for lifelong immunosuppression.
In this Research Topic, we welcome the submission of Original Research, Review, Minireview, Case Report, Opinion and Methods articles that address, but are not limited to, the following subtopics:
1) The mechanism of autoantigen presentation, whether overt presentation leads to hepatocyte and bile duct inflammation in the manner of autoimmunity
2) The role of specific HLA profiles, either at a heterozygous or homozygous gene level or at the haplotype level on autoantigen presentation
3) Factors and agents leading to enhancing or decreasing the antigen presentation process
4) Methods and approaches to interfere with the process of antigen presentation, such as manipulation of immune cells with immunoregulatory properties, including Treg, B regulatory (Breg), NK cells and mucosal associated invariant T (MAIT) cells, and peptide vaccination
This Research Topic aims to establish the links between HLA genes and clinical manifestation in various racial groups, especially in rarely investigated populations, including African American, Central American and South American groups. This will provide insight into the impact of HLA genes on autoantigen presentation, with a particular focus on its influence on autoantigen specific immunoregulation and the possible intervention to block overt antigen presentation and to establish effective immunosuppression. The final goal in this field is to restore the liver tolerogenic status by the development of therapeutic approaches, such as a peptide vaccine in order to replace the current treatment of lifelong immunosuppressive steroids.
In this Research Topic, we welcome submissions of Original Research, Review, Minireview, Case Report, Opinion and Methods articles that address, but are not limited to, the following subtopics:
1) The mechanism of autoantigen presentation, whether overt presentation leads to hepatocyte and bile duct inflammation in the manner of autoimmunity
2) The role of specific HLA profiles, either at a heterozygous or homozygous gene level or at the haplotype level on autoantigen presentation
3) Factors and agents leading to enhancing or decreasing the antigen presentation process
4) Methods and approaches to interfere with the process of antigen presentation, such as manipulation of immune cells with immunoregulatory properties, including Treg, Breg, NK cells and mucosal associated invariant T (MAIT) cells, and peptide vaccination
The liver is a tolerogenic organ. Despite receiving both dietary and microbial antigens from its dual blood supply comprising arterial blood and blood from the gut via the portal vein, it maintains tolerance to these foreign antigens through its unique and powerful immune system, working in harmony to protect liver parenchyma cells and bile ducts. However, when this tolerogenic status breaks down, autoimmune liver diseases [autoimmune hepatitis (AIH)/autoimmune sclerosing cholangitis (ASC)/primary biliary cholangitis (PBC)] occur. The possible triggers leading to tolerance breakdown include certain viral infections and drugs. There are also certain predisposition HLA genes such as HLA DRB1*0301 (DR3), - 0701 (DR7), -1301 (DR13) and haplotype HLA A1-B8-DR3 in patients of Northern European ancestry and DR4 in Chinese and Japanese for AIH/ASC and HLA DRB1*0801 for PBC. Patients possessing these genes have more severe liver disease than those without. In addition, there is preliminary data showing that patients with AIH/ASC with the HLA-DR3/DR7/DR13 genes display Treg frequency lower than non-HLA-DR3/DR7/DR13 subjects. This could indicate that autoimmune disease predisposition HLA genes are associated with overt autoantigen presentation and hamper immunoregulation, leading to perpetuation of liver autoimmunity. However, the exact mechanisms played by HLA genes in liver specific autoimmunity remains unknown and needs to be explored.
This Research Topic aims to establish the links between HLA genes and clinical manifestations in a diverse population so that it is inclusive of different races and ethnicities. Secondly, the aim is to provide insight into how HLA genes impact autoantigen presentation, with a particular focus on autoantigen specific immunoregulation. This may allow tailoring of future therapeutic interventions to block overt antigen presentation and thereby establish more effective control of autoimmune disease. The ultimate goal is to restore the liver tolerogenic status by the development of novel therapeutic approaches, including peptide vaccines, in order to replace the current need for lifelong immunosuppression.
In this Research Topic, we welcome the submission of Original Research, Review, Minireview, Case Report, Opinion and Methods articles that address, but are not limited to, the following subtopics:
1) The mechanism of autoantigen presentation, whether overt presentation leads to hepatocyte and bile duct inflammation in the manner of autoimmunity
2) The role of specific HLA profiles, either at a heterozygous or homozygous gene level or at the haplotype level on autoantigen presentation
3) Factors and agents leading to enhancing or decreasing the antigen presentation process
4) Methods and approaches to interfere with the process of antigen presentation, such as manipulation of immune cells with immunoregulatory properties, including Treg, B regulatory (Breg), NK cells and mucosal associated invariant T (MAIT) cells, and peptide vaccination
This Research Topic aims to establish the links between HLA genes and clinical manifestation in various racial groups, especially in rarely investigated populations, including African American, Central American and South American groups. This will provide insight into the impact of HLA genes on autoantigen presentation, with a particular focus on its influence on autoantigen specific immunoregulation and the possible intervention to block overt antigen presentation and to establish effective immunosuppression. The final goal in this field is to restore the liver tolerogenic status by the development of therapeutic approaches, such as a peptide vaccine in order to replace the current treatment of lifelong immunosuppressive steroids.
In this Research Topic, we welcome submissions of Original Research, Review, Minireview, Case Report, Opinion and Methods articles that address, but are not limited to, the following subtopics:
1) The mechanism of autoantigen presentation, whether overt presentation leads to hepatocyte and bile duct inflammation in the manner of autoimmunity
2) The role of specific HLA profiles, either at a heterozygous or homozygous gene level or at the haplotype level on autoantigen presentation
3) Factors and agents leading to enhancing or decreasing the antigen presentation process
4) Methods and approaches to interfere with the process of antigen presentation, such as manipulation of immune cells with immunoregulatory properties, including Treg, Breg, NK cells and mucosal associated invariant T (MAIT) cells, and peptide vaccination
