Liver immunity, autoimmunity, and inborn errors of immunity

Abstract

The liver is the front line organ of the immune system. The liver contains the largest collection of phagocytic cells in the body that detect both pathogens that enter through the gut and endogenously produced antigens. This is possible by the highly developed differentiation capacity of the liver immune system between self-antigens or non-self-antigens, such as food antigens or pathogens. As an immune active organ, the liver functions as a gatekeeping barrier from the outside world, and it can create a rapid and strong immune response, under unfavorable conditions. However, the liver's assumed immune status is anti-inflammatory or immuno-tolerant. Dynamic interactions between the numerous populations of immune cells in the liver are key for maintaining the delicate balance between immune screening and immune tolerance. The anatomical structure of the liver can facilitate the preparation of lymphocytes, modulate the immune response against hepatotropic pathogens, and contribute to some of its unique immunological properties, particularly its capacity to induce antigen-specific tolerance. Since liver sinusoidal endothelial cell is fenestrated and lacks a basement membrane, circulating lymphocytes can closely contact with antigens, displayed by endothelial cells, Kupffer cells, and dendritic cells while passing through the sinusoids. Loss of immune tolerance, leading to an autoaggressive immune response in the liver, if not controlled, can lead to the induction of autoimmune or autoinflammatory diseases. This review mentions the unique features of liver immunity, and dysregulated immune responses in patients with autoimmune liver diseases who have a close association with inborn errors of immunity have also been the emphases.

Keywords: Autoimmune liver diseases; Autoimmunity; Autoinflamation; Immune tolerance; Inborn errors of immunity; Liver immunity.

Figure 1

Cell composition of the healthy liver. ILC: Innate lymphoid cells; DC: Dendritic cells; LSEC: Liver sinusoidal endothelial cells; NK: Natural killer; NKT: Natural killer T.

Figure 2

Model of pathogenic mechanisms in primary biliary cholangitis. APC: Antigen presenting cell; DC: Dendritic cell; NK: Natural killer; IL: Interleukin; TNF: Tumor necrosis factor; TGF-β: Transforming growth factor β; IFN-γ: Interferon-gamma; PPAR: Peroxisome proliferator-activated receptor; AMA: Anti-mitochondrial antibody.

Figure 3

Pathogenic pathways of autoimmune hepatitis. APC: Antigen-presenting cell; CTL: Cytotoxic T lymphocyte; Mac: Macrophage; IL: Interleukin; TNF: Tumor necrosis factor; MHC: Major histocompatibility complex; TGF-β: Transforming growth factor β; IFN-γ: Interferon-gamma.