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Elife. 2019 Aug 15;8. pii: e48378. doi: 10.7554/eLife.48378.

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

Author information

1
Department of Ophthalmology, Duke University Medical Center, Durham, United States.
2
Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, United States.
3
Department of Immunology, Duke University Medical Center, Durham, United States.
4
Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, United States.

Abstract

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.

KEYWORDS:

HSV-1; complement; cornea; graft vs. host disease; immunology; infectious disease; inflammation; microbiology; mouse; neuropathy

PMID:
31414985
DOI:
10.7554/eLife.48378
Free PMC Article

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