{"doi":"10.1073/pnas.2407648121","title":"CD4 <sup>+</sup> T cells drive corneal nerve damage but not epitheliopathy in an acute aqueous-deficient dry eye model","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.","journal":"Proceedings of the National Academy of Sciences","year":2024,"id":427152,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":16,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9569,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1227840,"name":"Manuela Pizzano","orcid":null,"position":1,"is_corresponding":false},{"id":1227841,"name":"Agostina Cernutto","orcid":null,"position":2,"is_corresponding":false},{"id":1227235,"name":"Florencia Sabbione","orcid":"0000-0002-9220-2210","position":3,"is_corresponding":false},{"id":1227236,"name":"Irene Keitelman","orcid":"0000-0002-7093-5712","position":4,"is_corresponding":false},{"id":1227842,"name":"Douglas Vera Aguilar","orcid":null,"position":5,"is_corresponding":false},{"id":1227237,"name":"Ariel Podhorzer","orcid":"0000-0002-4861-5333","position":6,"is_corresponding":false},{"id":391822,"name":"Federico Fuentes","orcid":null,"position":7,"is_corresponding":false},{"id":1219805,"name":"Celia Corral-Vázquez","orcid":"0000-0002-0621-4590","position":8,"is_corresponding":false},{"id":412057,"name":"Mauricio Guzmán","orcid":"0000-0002-4447-2064","position":9,"is_corresponding":false},{"id":1227843,"name":"Mirta Giordano","orcid":null,"position":10,"is_corresponding":false},{"id":1227238,"name":"Analía Trevani","orcid":"0000-0001-7254-1082","position":11,"is_corresponding":false},{"id":283912,"name":"Cintia S. de Paiva","orcid":"0000-0002-9057-5494","position":12,"is_corresponding":false},{"id":647820,"name":"Jeremías G. Galletti","orcid":"0000-0002-5118-2540","position":13,"is_corresponding":false},{"id":1227234,"name":"Alexia Vereertbrugghen","orcid":"0000-0002-4210-2916","position":0,"is_corresponding":true}],"reference_count":85,"raw_metadata":null,"created_at":"2026-07-19T01:58:47.805440Z","pmid":"39560641","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}