CD93 regulates central nervous system inflammation in two mouse models of autoimmune encephalomyelitis

Area of Science:

• Neuroimmunology
• Central Nervous System (CNS) Inflammation

Background:

• Microglia and other non-professional immune cells manage pathogen and debris removal in CNS injuries via pro-inflammatory pathways.
• Mechanisms governing these inflammatory responses in the CNS are not well understood.

Purpose of the Study:

• To investigate the role of CD93 (complement C1q receptor/AA4 stem cell marker) in regulating neuroinflammation.
• To evaluate CD93's function in experimental autoimmune encephalomyelitis (EAE) and antibody-dependent EAE (AD-EAE) models.

Main Methods:

• Utilized wild-type and CD93 knockout mouse models for MOG-induced EAE and AD-EAE.
• Analyzed CD93 expression in various CNS cell types (neurons, microglia, endothelial cells, astrocytes, oligodendrocytes).
• Assessed inflammatory markers, immune cell infiltration (M1 macrophages), microglial activation, blood-brain barrier integrity, and neuronal damage.

Main Results:

• CD93 is expressed by neurons, endothelial cells, and microglia, but not astrocytes or oligodendrocytes.
• CD93-deficient mice exhibited exacerbated brain and spinal cord inflammation in both EAE models.
• Enhanced neuroinflammation in CD93-/- mice included increased M1 macrophages, activated microglia, blood-brain barrier disruption, and greater neuronal injury.

Conclusions:

• CD93 plays a crucial role in regulating neuroinflammatory processes within the central nervous system.
• CD93 acts as a key neuro-immune regulator, controlling the severity of CNS inflammation and associated damage.