Complement and CD4⁺ T cells drive context-specific corneal sensory neuropathy.

Area of Science:

• Neuroimmunology
• Ophthalmology
• Complement System

Background:

• Peripheral nervous system (PNS) diseases, including sensory neuropathies, can involve nerve damage.
• The role of complement system dysregulation in the pathogenesis of sensory neuropathies is not fully understood.
• Ocular infections, such as HSV-1, often lead to sensory nerve damage.

Purpose of the Study:

• To investigate the role of the complement system, specifically C3, in sensory nerve damage.
• To determine the involvement of CD4 T cells in complement-mediated nerve pathology.
• To explore the C3/CD4 T cell axis in different ocular disease models.

Main Methods:

• Utilized mouse models of ocular HSV-1 infection and ocular graft-versus-host disease (GVHD).
• Employed genetic and pharmacologic targeting strategies to investigate C3 and CD4 T cell functions.
• Assessed morphological and functional levels of sensory nerve damage.

Main Results:

• Demonstrated a central role for C3 in sensory nerve damage in ocular HSV-1 infection.
• Identified CD4 T cells as critical mediators of complement-driven nerve damage.
• Showed that the C3/CD4 T cell axis also contributes to corneal sensory nerve damage in a GVHD model.
• Found this neuroimmune pathology was not present in a T-dependent allergic eye disease (AED) model.

Conclusions:

• Complement component C3 plays a significant role in CD4 T cell-dependent corneal nerve damage across multiple disease etiologies.
• The findings suggest that complement-targeted therapeutics could be a viable strategy for mitigating sensory neuropathies.
• This research elucidates a specific neuroinflammatory pathway involving complement and T cells in ocular diseases.