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