Complement and CD4+ T cells drive context-specific corneal sensory neuropathy.
Whether complement dysregulation directly contributes to the pathogenesis of peripheral nervous system diseases, including sensory neuropathies, is unclear. We addressed this important question in a mouse model of ocular HSV-1 infection, where sensory nerve damage is a common clinical problem. Through genetic and pharmacologic targeting, we uncovered a central role for C3 in sensory nerve damage at the morphological and functional levels. Interestingly, CD4 T cells were central in facilitating this complement-mediated damage. This same C3/CD4 T cell axis triggered corneal sensory nerve damage in a mouse model of ocular graft-versus-host disease (GVHD). However, this was not the case in a T-dependent allergic eye disease (AED) model, suggesting that this inflammatory neuroimmune pathology is specific to certain disease etiologies. Collectively, these findings uncover a central role for complement in CD4 T cell-dependent corneal nerve damage in multiple disease settings and indicate the possibility for complement-targeted therapeutics to mitigate sensory neuropathies.
Duke Scholars
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Related Subject Headings
- Sensory Receptor Cells
- Neurodegenerative Diseases
- Mice
- Keratitis, Herpetic
- Immunologic Factors
- Disease Models, Animal
- Complement C3
- CD4-Positive T-Lymphocytes
- Animals
- 42 Health sciences
Citation
Published In
DOI
EISSN
Publication Date
Volume
Location
Related Subject Headings
- Sensory Receptor Cells
- Neurodegenerative Diseases
- Mice
- Keratitis, Herpetic
- Immunologic Factors
- Disease Models, Animal
- Complement C3
- CD4-Positive T-Lymphocytes
- Animals
- 42 Health sciences