Purpose: Novel paradigms have broadened our understanding of mechanisms through which complement mediates allograft inflammation/injury. Herein we review advances in the field and highlight therapeutic implications.
Recent Findings: Pre-clinical and translational human trials have elucidated complement-dependent mechanisms of post-transplant ischemia-reperfusion (I/R) injury. Immune cell-derived, and intracellular, complement activation are newly linked to proinflammatory T cell immunity relevant to allograft rejection. Complement-induced immune regulation, including C5a ligation of C5a receptor 2 on T cells, C5a/C5a receptor 1 interactions on regulatory myeloid cells, and C1q binding to CD8 T cells can inhibit proinflammatory T cells and/or prolong murine allograft survival. Pilot trials of complement inhibition to treat/prevent human I/R- or antibody-initiated allograft injury show promise.
Summary: The complement system participates in allograft injury through multiple context- dependent mechanisms involving various components and receptors. These new insights along with development and implementation of individualized complement inhibitory strategies have potential to improve transplant outcomes.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6822566 | PMC |
| http://dx.doi.org/10.1007/s40472-019-0224-2 | DOI Listing |
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