Complement and CD4+ T cells drive context-specific corneal sensory neuropathy.
Published online
Journal Article
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.
Full Text
Duke Authors
Cited Authors
- Royer, DJ; Echegaray-Mendez, J; Lin, L; Gmyrek, GB; Mathew, R; Saban, DR; Perez, VL; Carr, DJ
Published Date
- August 15, 2019
Published In
Volume / Issue
- 8 /
PubMed ID
- 31414985
Pubmed Central ID
- 31414985
Electronic International Standard Serial Number (EISSN)
- 2050-084X
Digital Object Identifier (DOI)
- 10.7554/eLife.48378
Language
- eng
Conference Location
- England