Abstract
The liver is a critical organ in controlling immune tolerance. In particular, it is now clear that targeting antigens for presentation by antigen presenting cells in the liver can induce immune tolerance to either autoantigens from the liver itself or tissues outside of the liver. Here we review immune mechanisms active within the liver that contribute both to the control of infectious diseases and tolerance to self-antigens. Despite its extraordinary capacity for tolerance induction, the liver remains a target organ for autoimmune diseases. In this review, we compare and contrast known autoimmune diseases of the liver. Currently patients tend to receive strong immunosuppressive treatments and, in many cases, these treatments are associated with deleterious side effects, including a significantly higher risk of infection and associated health complications. We propose that, in future, antigen-specific immunotherapies are adopted for treatment of liver autoimmune diseases in order to avoid such adverse effects. We describe various therapeutic approaches that either are in or close to the clinic, highlight their mechanism of action and assess their suitability for treatment of autoimmune liver diseases.
Highlights
In future, antigen-specific immunotherapies are adopted for treatment of liver autoimmune diseases in order to avoid such adverse effects
Autoimmune liver disease (AILD) patients commonly present other autoimmune diseases, suggesting that immune dysregulation is not isolated to the liver in these cases
This follows evidence that treatment of experimental animals with antigens can lead to amelioration of disease [146]. These approaches target CD4 T cell recognition of self-antigens. This is because CD4 T cells control the generation of all of the tissue damaging mechanisms associated with autoimmunity including pathogenic autoantibodies, antigen-driven inflammation and self-antigen specific CD8 T cells
Summary
We review immune mechanisms active within the liver that contribute both to the control of infectious diseases and tolerance to self-antigens. In future, antigen-specific immunotherapies are adopted for treatment of liver autoimmune diseases in order to avoid such adverse effects. Antigen-presentation and costimulatory capacity of resting APC in the liver is generally low, contributing to the liver’s state of active tolerance.
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