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.
['Royer|Derek J|DJ|0000-0002-8476-1784', 'Echegaray-Mendez|Jose|J|', 'Lin|Liwen|L|', 'Gmyrek|Grzegorz B|GB|', 'Mathew|Rose|R|', 'Saban|Daniel R|DR|', 'Perez|Victor L|VL|', 'Carr|Daniel Jj|DJ|']
D000818:Animals D015496:CD4-Positive T-Lymphocytes D003176:Complement C3 D004195:Disease Models, Animal D007155:Immunologic Factors D016849:Keratitis, Herpetic D051379:Mice D019636:Neurodegenerative Diseases D011984:Sensory Receptor Cells
complement neuropathy mouse HSV-1 cornea graft vs. host disease immunology infectious disease inflammation microbiology