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.

中文翻译：

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在急性房水缺陷型干眼症模型中，CD4 + T 细胞驱动角膜神经损伤，但不驱动上皮病变


干眼症 （DED） 的特征是泪膜功能失调，其中角膜上皮及其丰富的神经受到眼部干燥和炎症的影响。尽管适应性免疫，特别是 CD4 + T 细胞在 DED 发病机制中发挥作用，但这些细胞对角膜上皮和神经损伤的确切贡献仍未确定。为了解决这个问题，我们探索了野生型 （WT） 和 T 细胞缺陷小鼠手术 DED 模型的进展。我们观察到适应性免疫缺陷小鼠与 WT 小鼠相比，除了没有功能和形态角膜神经变化、三叉神经节中神经损伤相关的转录组特征和持续的泪液细胞因子水平外，DED 的各个方面都发生了。CD4 + T 细胞从 WT DED 小鼠过继转移到 T 细胞缺陷小鼠再现了角膜神经损伤，但未再现上皮病。相反，仅用初始 CD4 + T 细胞重构的 T 细胞缺陷小鼠在 DED 诱导后发生角膜神经损伤和上皮病变，从而复制 WT DED 表型。总的来说，我们的数据表明，虽然角膜神经病变是由 DED 中的 CD4 + T 细胞驱动的，但角膜上皮损伤的发展独立于适应性免疫反应。这些发现对目前用于 DED 的 T 细胞靶向疗法具有意义。