Novel Role of Complement Factor H in Macrophages

Authors: Aum Champaneri, Jessy Alexander

SUNY Campus: SUNY Buffalo

Presentation Type: Poster

Location: Old Union Hall

Presentation #: 53

Timeslot: Session B 10:15-11:15 AM

Abstract: The protein Factor H (FH) is primarily known for controlling the complement system, an important arm of the innate immune system, preventing it from attacking the body’s own tissues. When FH is absent, diseases like dense deposit disease and age-related macular degeneration can develop, causing an influx of immune cells called macrophages in the affected areas. An earlier study from our lab revealed that depletion of macrophages reduced disease pathology in a model of dense deposit disease. While FH is mostly produced by the liver, it is also made by macrophages, though its specific role in these cells is not completely understood—until now. In this study, we uncovered a surprising new function of FH in macrophages. We found that FH regulates genes involved in cell growth and inflammation. Without FH, macrophages become hyperactive, showing increased growth, movement, and migration, while reducing their ability to clear harmful substances. Additionally, FH-deficient macrophages display metabolic changes, relying less on energy processes like oxidative phosphorylation and glycolysis. We also discovered that FH influences macrophage behaviour through a signalling pathway involving C3a and its receptor (C3aR), which affects calcium levels and the protein TRPM7. Blocking TRPM7 reduced macrophage growth, suggesting new treatment possibilities for diseases like kidney disorders and other inflammatory conditions.