Tissue targeting is a promising complement regulation strategy, which provides a safer and considerably more effective therapeutic approach compared with a systemic (untargeted) complement inhibition. One such targeting approach involves linking a complement inhibitor to a fragment of CR2 that recognizes C3 activation products deposited at sites of complement activation (Fig. 2). Complement inhibitors such as Crry, FH, or CD59 will go directly to the complement-attacked tissue after systemic infusion and locally inhibit complement without compromising the systemic complement function [55]. CR2-Crry, a site-targeted complement inhibitor, can suppress C3 activation through inhibition of C3 convertase, resulting in a reduction in the levels of C3a, C3b, and Asp. A recent study showed that suppression of C3 activation can protect against the injury of steatosis and inflammation in ALD [32]. Therefore, targeted complement inhibitors may become a potential drug to protect against both infiammatory response syndrome and hepatic steatosis for AFLD patients (Fig. 3) [32].
