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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2024,11,26]]},"abstract":"<jats:p>\n                    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\n                    <jats:sup>+<\/jats:sup>\n                    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\n                    <jats:sup>+<\/jats:sup>\n                    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\u00efve CD4\n                    <jats:sup>+<\/jats:sup>\n                    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\n                    <jats:sup>+<\/jats:sup>\n                    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.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2407648121","type":"journal-article","created":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T10:46:41Z","timestamp":1732013201000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":25,"title":["CD4\n                    <sup>+<\/sup>\n                    T cells drive corneal nerve damage but not epitheliopathy in an acute aqueous-deficient dry eye model"],"prefix":"10.1073","volume":"121","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4210-2916","authenticated-orcid":false,"given":"Alexia","family":"Vereertbrugghen","sequence":"first","affiliation":[{"name":"Innate Immunity Laboratory, Institute of Experimental Medicine (National Scientific and Technical Research Council\/National Academy of Medicine of Buenos Aires), Buenos Aires 1425, 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Vereertbrugghen M. Pizzano J. G. Galletti Data from \u201cBulk RNA-seq of trigeminal ganglia from C57BL\/6 (wild-type) and Rag1KO mice with dry eye (extraorbital lacrimal gland excision model) versus sham-operated controls.\u201d ArrayExpress. https:\/\/www.ebi.ac.uk\/biostudies\/arrayexpress\/studies\/E-MTAB-13945. 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