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

  1. Derek J Royer  Is a corresponding author
  2. Jose Echegaray-Mendez
  3. Liwen Lin
  4. Grzegorz B Gmyrek
  5. Rose Mathew
  6. Daniel R Saban
  7. Victor L Perez
  8. Dan Carr
  1. Duke University, United States
  2. University of Oklahoma Health Sciences Center, 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.

Data availability

Data generated during this study are included in the manuscript.

Article and author information

Author details

  1. Derek J Royer

    Department of Ophthalmology, Duke University, Durham, United States
    For correspondence
    Derek.Royer@Duke.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8476-1784
  2. Jose Echegaray-Mendez

    Department of Ophthalmology, Duke University, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Liwen Lin

    Department of Ophthalmology, Duke University, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Grzegorz B Gmyrek

    Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Rose Mathew

    Department of Ophthalmology, Duke University, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Daniel R Saban

    Department of Ophthalmology, Duke University, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Victor L Perez

    Department of Ophthalmology, Duke University, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Dan Carr

    Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, United States
    Competing interests
    The authors declare that no competing interests exist.

Funding

National Eye Institute (R01 EY021238)

  • Dan Carr

National Eye Institute (P30 EY021725)

  • Dan Carr

National Eye Institute (R01 EY021798)

  • Daniel R Saban

National Eye Institute (R01 EY024484)

  • Victor L Perez

National Eye Institute (P30 EY005722)

  • Daniel R Saban

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. Research was performed in accordance with protocols approved by institutional care and use committees at the University of Oklahoma Health Sciences Center (Protocol number 160-014-NSI) and Duke University (Protocol numbers A061-18-03 and A034-18-01).

Reviewing Editor

  1. Isaac M Chiu, Harvard Medical School, United States

Publication history

  1. Received: May 10, 2019
  2. Accepted: August 15, 2019
  3. Accepted Manuscript published: August 15, 2019 (version 1)
  4. Version of Record published: October 8, 2019 (version 2)

Copyright

© 2019, Royer et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Derek J Royer
  2. Jose Echegaray-Mendez
  3. Liwen Lin
  4. Grzegorz B Gmyrek
  5. Rose Mathew
  6. Daniel R Saban
  7. Victor L Perez
  8. Dan Carr
(2019)
Complement and CD4+ T cells drive context-specific corneal sensory neuropathy
eLife 8:e48378.
https://doi.org/10.7554/eLife.48378

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