The recognition of the unique phenotype of intestinal and liver autoimmune diseases has led research into uncovering the underlying pathogenic mechanisms. A variety of mechanisms have been proposed in an effort to determine the unifying roles of the phenotypes of intestinal and liver autoimmune diseases, and also the crosstalk of the intestinal and liver diseases and their comorbidity.
The intestinal epithelium forms a dynamic physicochemical barrier to maintain immune homeostasis. The epithelium in the small intestine has integral, permeable layers forming a complete mucosal barrier. Intestinal barrier includes gut microbiota, mucus layer, epithelial cells and infiltrating immune cell populations. Although the small intestine and colon differ in the gross structure and composition of intestinal epithelial cells, they share overall integrity to build intestinal homeostasis. Defects in gut barriers in the pathogenesis of human intestinal diseases indicate dysfunction of tissue homeostasis. Secretory epithelial cells, tight and adherent junctions will lose control over internal and external invaders. Defects in the gut barrier are associated with several human diseases as inflammatory bowel diseases (IBD), autoimmune liver diseases or neurologic diseases. Patients with IBD suffer from incomplete intestinal permeability, pro-inflammatory cytokines, and alterations of environmental sensors. Current IBD therapeutic strategies aim to restore the gut barrier function.
Liver is an inherent site of immune tolerance which induces autoimmunity. As a lymphoid organ, it continuously undergoes the uptake of bloodborne pathogens and metabolite detoxification. It acts as a barrier towards microbial and other antigens. Autoimmune liver diseases are a panel of chronic inflammatory diseases caused by abnormal immune attack against hepatocytes or bile duct epithelial cell, including autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), IgG4-related sclerosing cholangitis (IgG4-SC), primary sclerosing cholangitis (PSC), and overlap syndromes.
Autoimmune liver diseases are commonly associated with other autoimmune diseases, such as inflammatory bowel diseases, including Crohn’s disease and ulcerative colitis (UC). A theory regarding the mechanism of PSC and gut barrier function is the “gut lymphocyte homing” hypothesis, which postulates that activated T cells from the intestine home in the liver initiate immune-mediated damage. The strong association of primary sclerosing cholangitis with inflammatory bowel diseases leads to a scenario that intestinal T cells are stimulated within intestine associated lymphoid tissues, and then are recruited to the hepatic tissues as a result of abnormal expression of their associated ligands and the chemotactic protein in the liver. Besides, the mutual interaction of both bile acids (BAs) and gut microbiota are associated with liver and gut disorders.
In this Research Topic, we encourage manuscripts that explore the basic mechanisms underlying the regulation of various subtypes of innate and adaptive immune cells, and immune milieu, of autoimmune intestine and liver diseases in vivo and in vitro, including but not limited to the functional interplay between immune cells and parenchymal cells. In addition, the influence of different metabolites and gut barriers such as bile acids, mucosal barrier, innate and adaptive immune cells and so on also deserves more attention. This Research Topic welcomes all Original Research and Review articles focusing on the unique pathogenesis and disease phenotypes of intestinal and liver autoimmunity, and the interaction between liver and the intestine to trigger a spark of hope for novel therapeutic strategies.
Welcome subtopics include, but are not limited to:
• The effects and mechanisms of various subtypes of innate and adaptive immune cells in experimental models of autoimmune liver and intestine diseases.
• Molecular mechanisms of the interactions between the immune system and hepatocytes/biliary and intestinal epithelial cells in the context of local microenvironment.
• Biomarkers and predictors of treatment response and prognosis of autoimmune liver or autoimmune intestine diseases from clinical data, such as key autoantigens, gut metabolites, changes in cytokines and pathways or their combination.
• New models for studying the relationship between autoimmune liver disease and intestinal autoimmune diseases in vivo and/or in vitro.
• Biomarkers, predictors and molecular mechanisms of dysimmunity or immunodeficiency in nodular regenerative hyperplasia (NRH) and immunodeficiencies in the intestine and liver
The recognition of the unique phenotype of intestinal and liver autoimmune diseases has led research into uncovering the underlying pathogenic mechanisms. A variety of mechanisms have been proposed in an effort to determine the unifying roles of the phenotypes of intestinal and liver autoimmune diseases, and also the crosstalk of the intestinal and liver diseases and their comorbidity.
The intestinal epithelium forms a dynamic physicochemical barrier to maintain immune homeostasis. The epithelium in the small intestine has integral, permeable layers forming a complete mucosal barrier. Intestinal barrier includes gut microbiota, mucus layer, epithelial cells and infiltrating immune cell populations. Although the small intestine and colon differ in the gross structure and composition of intestinal epithelial cells, they share overall integrity to build intestinal homeostasis. Defects in gut barriers in the pathogenesis of human intestinal diseases indicate dysfunction of tissue homeostasis. Secretory epithelial cells, tight and adherent junctions will lose control over internal and external invaders. Defects in the gut barrier are associated with several human diseases as inflammatory bowel diseases (IBD), autoimmune liver diseases or neurologic diseases. Patients with IBD suffer from incomplete intestinal permeability, pro-inflammatory cytokines, and alterations of environmental sensors. Current IBD therapeutic strategies aim to restore the gut barrier function.
Liver is an inherent site of immune tolerance which induces autoimmunity. As a lymphoid organ, it continuously undergoes the uptake of bloodborne pathogens and metabolite detoxification. It acts as a barrier towards microbial and other antigens. Autoimmune liver diseases are a panel of chronic inflammatory diseases caused by abnormal immune attack against hepatocytes or bile duct epithelial cell, including autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), IgG4-related sclerosing cholangitis (IgG4-SC), primary sclerosing cholangitis (PSC), and overlap syndromes.
Autoimmune liver diseases are commonly associated with other autoimmune diseases, such as inflammatory bowel diseases, including Crohn’s disease and ulcerative colitis (UC). A theory regarding the mechanism of PSC and gut barrier function is the “gut lymphocyte homing” hypothesis, which postulates that activated T cells from the intestine home in the liver initiate immune-mediated damage. The strong association of primary sclerosing cholangitis with inflammatory bowel diseases leads to a scenario that intestinal T cells are stimulated within intestine associated lymphoid tissues, and then are recruited to the hepatic tissues as a result of abnormal expression of their associated ligands and the chemotactic protein in the liver. Besides, the mutual interaction of both bile acids (BAs) and gut microbiota are associated with liver and gut disorders.
In this Research Topic, we encourage manuscripts that explore the basic mechanisms underlying the regulation of various subtypes of innate and adaptive immune cells, and immune milieu, of autoimmune intestine and liver diseases in vivo and in vitro, including but not limited to the functional interplay between immune cells and parenchymal cells. In addition, the influence of different metabolites and gut barriers such as bile acids, mucosal barrier, innate and adaptive immune cells and so on also deserves more attention. This Research Topic welcomes all Original Research and Review articles focusing on the unique pathogenesis and disease phenotypes of intestinal and liver autoimmunity, and the interaction between liver and the intestine to trigger a spark of hope for novel therapeutic strategies.
Welcome subtopics include, but are not limited to:
• The effects and mechanisms of various subtypes of innate and adaptive immune cells in experimental models of autoimmune liver and intestine diseases.
• Molecular mechanisms of the interactions between the immune system and hepatocytes/biliary and intestinal epithelial cells in the context of local microenvironment.
• Biomarkers and predictors of treatment response and prognosis of autoimmune liver or autoimmune intestine diseases from clinical data, such as key autoantigens, gut metabolites, changes in cytokines and pathways or their combination.
• New models for studying the relationship between autoimmune liver disease and intestinal autoimmune diseases in vivo and/or in vitro.
• Biomarkers, predictors and molecular mechanisms of dysimmunity or immunodeficiency in nodular regenerative hyperplasia (NRH) and immunodeficiencies in the intestine and liver
