CD4+ T cells drive corneal nerve damage but not epitheliopathy in an acute aqueous- deficient dry eye model

• 成果类型: Article
• 署名作者: Vereertbrugghen, Alexia; Pizzano, Manuela; Cernutto, Agostina; Sabbione, Florencia; Keitelman, Irene A.; Aguilar, Douglas Vera; Podhorzer, Ariel; Fuentes, Federico; Corral-Vazquez, Celia; Guzman, Mauricio; Giordano, Mirta N.; de Paiva, Cintia S.; Downie, Laura E.; Nathans, Jeremy
• 署名单位: Buenos Aires National Academy of Medicine; Buenos Aires National Academy of Medicine; Buenos Aires National Academy of Medicine; Hospital del Mar Research Institute; Hospital del Mar; Baylor College of Medicine
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-15333
• DOI: 10.1073/pnas.24076481211
• 发表日期: 2024-11-26
• 关键词: lacrimal gland excision; ocular-surface; interferon-gamma; squamous metaplasia; neuropathic pain; disease; expression; sjogrens; conjunctiva; activation

摘要

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 na & iuml;ve 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.