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

Author:

Royer Derek J12ORCID,Echegaray-Mendez Jose1,Lin Liwen1,Gmyrek Grzegorz B2,Mathew Rose1,Saban Daniel R13,Perez Victor L1,Carr Daniel JJ24

Affiliation:

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.

Funder

National Eye Institute

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

Reference130 articles.

1. Classical dendritic cells mediate fibrosis directly via the retinoic acid pathway in severe eye allergy;Ahadome;JCI Insight,2016

2. Alloimmunity and tolerance in corneal transplantation;Amouzegar;The Journal of Immunology,2016

3. Neuropathic symptoms of the ocular surface: dryness, pain, and itch;Andersen;Current Opinion in Allergy and Clinical Immunology,2017

4. Pain and immunity: implications for host defence;Baral;Nature Reviews Immunology,2019

5. Differential expression of the complement regulatory proteins in the human eye;Bora;Investigative Ophthalmology & Visual Science,1993

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