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

• DOI: 10.7554/elife.48378
• Publication Date: 2019-08-15T12:00:24Z
• Authors: Derek J Royer; Jose Echegaray-Me...; Liwen Lin; Grzegorz B Gmyrek; Rose Mathew; Daniel R Saban; Victor L Perez; Daniel JJ Carr
• Keywords: Pathogenesis; Sensory nerve

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 ocular HSV-1 infection, where nerve damage common clinical problem. Through genetic and pharmacologic targeting, we uncovered central role for C3 at morphological functional levels. Interestingly, CD4 T cells were facilitating complement-mediated damage. This same C3/CD4 cell axis triggered corneal graft-versus-host disease (GVHD). However, was not case T-dependent allergic eye (AED) model, suggesting that inflammatory neuroimmune pathology specific certain etiologies. Collectively, these findings uncover cell-dependent multiple settings indicate possibility complement-targeted therapeutics mitigate neuropathies.