Complement factor H, a marker of self protects against experimental autoimmune encephalomyelitis

Area of Science:

• Neuroimmunology
• Complement System Biology

Background:

• The CNS innate immune response is a critical balance between protection and neurotoxicity.
• Identifying regulatory mechanisms of CNS innate immunity is key for novel therapeutic strategies.
• Neuroimmune regulatory proteins, like "don't eat me" signals, modulate immune responses.

Purpose of the Study:

• To identify the role of complement regulator factor H (fH) in controlling neuroinflammation.
• To investigate fH's therapeutic potential in CNS inflammatory diseases.

Main Methods:

• Utilized an acute mouse model of Ab-dependent experimental autoimmune encephalomyelitis (EAE).
• Assessed fH expression in primary neurons, neuronal cell lines, microglia, and astrocytes.
• Administered exogenous human fH to EAE mice and evaluated clinical scores, inflammation, and demyelination.

Main Results:

• Factor H (fH) is abundantly expressed by neurons and also by microglia and astrocytes in the CNS.
• fH expression was significantly reduced in inflammatory EAE settings.
• Exogenous fH administration reduced clinical scores, inflammation, and demyelination in EAE mice.
• fH protected neurons from complement opsonization, axonal injury, and leukocyte infiltration.

Conclusions:

• Factor H (fH) plays a key regulatory role in neuroprotection within the CNS.
• fH demonstrates significant therapeutic potential for chronic CNS inflammatory diseases.