About this Research Topic

Background

The complement system is highly conserved throughout evolution, which plays a key role in pathogen immunosurveillance and tissue homeostasis. The complement system comprises an extensive network of fluid-phase and membrane-bound glycoproteins, cofactors, receptors, and regulatory proteins, including more than 50 members, and engages in innate immune recognition, adaptive cell stimulation, and pro-inflammatory effector responses. Most of the serum complement components are produced in the liver, and lots of complement receptors are expressed in hepatic parenchymal cells and non-parenchymal cells, including liver cells, Kupffer cells, hepatic stellate cells, etc. The liver is a central immunological organ with high exposure to circulating antigens and endotoxins from the gut microbiota. The complement system was demonstrated to play essential roles in maintaining the immune microenvironment in the liver. In liver homeostasis, many mechanisms ensure suppression of immune responses, resulting in immune tolerance. Meanwhile, the liver can rapidly activate immunity in response to infections or tissue damage. Depending on the underlying liver diseases, such as viral hepatitis, alcohol-related liver injury, non-alcoholic steatohepatitis, cholestatic liver injury, or surgery, different triggers mediate different immune-cell activation, which may result in an inflammatory microenvironment. Excessive inflammation in the absence of infection leads to sterile liver injury, tissue damage, and remodeling; insufficient immunity allows for chronic infection and cancer. Although the correlations between complement activation and various liver diseases have been reported to a certain degree, the underlying mechanisms remain elusive. Besides, more than 20 candidate drugs that target different stages of the complement cascade are currently being tested in clinical trials, and additional agents are in preclinical development. Despite the encouraging progress in drug discovery, translation of these observations into therapeutic strategies remains challenging and requires differential considerations, including the appropriate selection of therapeutic targets and patient populations in each disorder, and the side effect and the efficacy of systemic inhibition of complement system, since it is an important host defense pathway.

In This Research Topic, we aim at exploring the role and underlying mechanisms of the complement system in the pathogenesis of various liver diseases, tending to provide more potential effective therapeutic targets and immunological predictive signatures for liver diseases. Furthermore, we also aim to provide a scientific forum for the latest and advanced research of developing a better targeting strategy of complement system for liver diseases.

We welcome submissions from both basic science and clinical research including Original Research, Systematic Review, Review, Mini Review, Perspective, Clinical trial, and Opinion covering, but not limited to, the following topics:

1. Complement activation and the pathogenesis of liver diseases

2. Complement-related risk signatures for liver diseases

3. Translational medicine on complement in liver diseases

4. Clinical trials focusing on complement regulation for liver diseases

5. Epigenetic changes in complement system during the pathogenesis of liver diseases

6. Immune-related adverse events of immunotherapy for liver diseases

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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