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

2019; eLife Sciences Publications Ltd; Volume: 8; Linguagem: Inglês

10.7554/elife.48378

2050-084X

Derek J. Royer, Jose Echegaray-Mendez, Liwen Lin, Grzegorz B. Gmyrek, Rose Mathew, Daniel R. Saban, Victor L. Perez, Daniel J.J. Carr,

Complement system in diseases

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.