Intracellular complement factor H protects neurons during CNS inflammation.

Intracellular complement factor H (CFH) protects neurons from inflammatory injury through a non-canonical role independent of complement C3. In single-nucleus RNA-sequencing of retinal ganglion cells from donors with multiple sclerosis and controls, CFH expression correlated strongly with resilience to degeneration. CFH was induced by inflammatory and oxidative stress, localized to the endoplasmic reticulum, limited reactive oxygen species accumulation and lipid peroxidation, and its protection depended on the C-terminal SCR20 domain in mice and humans.