Language
English
Publication Date
11-26-2024
Journal
Proceedings of the National Academy of Sciences of the United States of America
DOI
10.1073/pnas.2407648121
PMID
39560641
PMCID
PMC11621630
PubMedCentral® Posted Date
11-19-2024
PubMedCentral® Full Text Version
Post-print
Abstract
Dry eye disease (DED) is characterized by a dysfunctional tear film in which the corneal epithelium and its abundant nerves are affected by ocular desiccation and inflammation. Although adaptive immunity and specifically CD4+ T cells play a role in DED pathogenesis, the exact contribution of these cells to corneal epithelial and neural damage remains undetermined. To address this, we explored the progression of a surgical DED model in wild-type (WT) and T cell-deficient mice. We observed that adaptive immune-deficient mice developed all aspects of DED comparably to WT mice except for the absence of functional and morphological corneal nerve changes, nerve damage-associated transcriptomic signature in the trigeminal ganglia, and sustained tear cytokine levels. Adoptive transfer of CD4+ T cells from WT DED mice to T cell-deficient mice reproduced corneal nerve damage but not epitheliopathy. Conversely, T cell-deficient mice reconstituted solely with naïve CD4+ T cells developed corneal nerve impairment and epitheliopathy upon DED induction, thus replicating the WT DED phenotype. Collectively, our data show that while corneal neuropathy is driven by CD4+ T cells in DED, corneal epithelial damage develops independently of the adaptive immune response. These findings have implications for T cell-targeting therapies currently in use for DED.
Keywords
Animals, Dry Eye Syndromes, CD4-Positive T-Lymphocytes, Mice, Disease Models, Animal, Epithelium, Corneal, Cornea, Tears, Mice, Inbred C57BL, Adoptive Transfer, Cytokines, Female, CD4 T cells. autoimmunity. cornea. neuropathy. ocular surface
Published Open-Access
yes
Recommended Citation
Vereertbrugghen, Alexia; Pizzano, Manuela; Cernutto, Agostina; et al., "CD4+ T Cells Drive Corneal Nerve Damage but Not Epitheliopathy in an Acute Aqueous-Deficient Dry Eye Model" (2024). Faculty and Staff Publications. 5514.
https://digitalcommons.library.tmc.edu/baylor_docs/5514