Differential expression of individual complement regulators in the brain and choroid plexus

Area of Science:

• Neuroimmunology
• Complement System Biology
• Cellular and Molecular Neuroscience

Background:

• The complement system (C) is a crucial part of innate immunity.
• Membrane-bound complement regulators control C activation.
• Expression of these regulators in the human central nervous system (CNS) is not fully understood.

Purpose of the Study:

• To investigate the expression of membrane-bound complement regulators in the human CNS.
• Specifically examining the temporal cortex and choroid plexus.
• To correlate expression patterns with neuronal susceptibility to complement-mediated damage.

Main Methods:

• Human temporal cortex and choroid plexus tissues were analyzed postmortem and surgically.
• Immunocytochemistry was used to detect protein expression of CD59, MCP, DAF, and CR1.
• RT-PCR and in situ hybridization identified mRNA expression of these complement regulators.

Main Results:

• Microglia strongly expressed CD59, MCP, and DAF; neurons expressed CD59 and MCP weakly, lacking DAF and CR1.
• Choroid plexus epithelium showed strong CD59, moderate MCP, and weak DAF expression; CR1 was found on Kolmer cells.
• mRNA analysis confirmed CD59, MCP, and DAF expression in the temporal cortex (glia, low neurons) and choroid plexus (epithelium), with CR1 mRNA only in the choroid plexus.

Conclusions:

• Neurons express low levels of CD59 and MCP and lack DAF and CR1, potentially explaining their susceptibility to complement-mediated damage in neurological diseases.
• The choroid plexus actively expresses complement regulators, suggesting a role in CNS immune surveillance and homeostasis.
• Findings highlight differential expression of complement regulators across CNS cell types, impacting neuroinflammation and disease pathogenesis.