The role of complement in liver injury, regeneration and transplantation

Abstract

The liver is both an immunologically complex and privileged organ. The innate immune system is a central player, and the complement system emerges as a pivotal part of liver homeostasis, in immune responses, and cross‐talk with other effector systems in both innate and adaptive immunity. The liver produces the majority of the complement proteins and is the home of important immune cells like the Kupffer cells. Liver immune responses are delicately tuned between tolerance to many antigens flowing in from the alimentary tract, a tolerance that probably makes the liver less prone to rejection than other solid organ transplants, and reaction to local injury, systemic inflammation and regeneration. Notably, complement is a double‐edged sword, as activation on the one hand is detrimental by inducing inflammatory tissue damage in e.g. ischemia‐reperfusion injury and transplant rejection, but on the other hand is beneficial for liver tissue regeneration. Therapeutic complement inhibition is rapidly developing for routine clinical treatment of several diseases. In the liver, targeted inhibition of damaged tissue may be a rational and promising approach to avoid further tissue destruction, and simultaneously preserve beneficial effects of complement in areas of proliferation. Here, we argue that complement is a key system to manipulate in the liver in several clinical settings including liver injury and regeneration after major surgery, and in preservation of the organ during transplantation.

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