{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T02:37:07Z","timestamp":1792291027430,"version":"4.4.0"},"reference-count":140,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T00:00:00Z","timestamp":1761782400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Dry eye disease (DED) is increasingly recognized as a condition driven by immune dysregulation at the ocular surface (OS). Chronic inflammation, mediated by aberrant activation of both innate and adaptive immune pathways, underlies disease progression and symptom persistence. Neuroimmune interactions further amplify OS inflammation, contributing to epithelial damage and impaired homeostatic regulation. This review summarizes current literature on the immunopathogenesis of DED, highlighting the complex interplay of molecular mechanisms of innate and adaptive immune activation, neuroimmune-mediated inflammation, and emerging molecular and cellular biomarkers. In addition, we examine existing and emerging therapeutic strategies that target these immune-molecular pathways, including precision immunomodulatory approaches, to inform future management of DED. By integrating mechanistic insights with clinical findings, this review aims to provide a comprehensive overview of the molecular mechanisms underlying the dysregulated immune response associated with DED.<\/jats:p>","DOI":"10.3390\/ijms262110583","type":"journal-article","created":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T01:23:59Z","timestamp":1761873839000},"page":"10583","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["The Immunobiology of Dry Eye Disease: A Review of the Pathogenesis, Regulation and Therapeutic Implications"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0195-3255","authenticated-orcid":false,"given":"Sarah Jacqueline","family":"Saram","sequence":"first","affiliation":[{"name":"Ministry of Health, 16 College Road College of Medicine Building and Singapore, Singapore 169854, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maya Natasha","family":"Thomas","sequence":"additional","affiliation":[{"name":"North Devon District Hospital, Royal Devon University Healthcare NHS Foundation Trust, Barnstaple EX31 4JB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo","family":"Feinberg","sequence":"additional","affiliation":[{"name":"West of England Eye Unit, Royal Devon University Healthcare NHS Foundation Trust, Exeter EX2 5DW, UK"},{"name":"Faculty of Health and Life Science, University of Exeter Medical School, Exeter EX1 2HZ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry W.","family":"Roberts","sequence":"additional","affiliation":[{"name":"West of England Eye Unit, Royal Devon University Healthcare NHS Foundation Trust, Exeter EX2 5DW, UK"},{"name":"Faculty of Health and Life Science, University of Exeter Medical School, Exeter EX1 2HZ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4320-2994","authenticated-orcid":false,"given":"Conor M.","family":"Ramsden","sequence":"additional","affiliation":[{"name":"West of England Eye Unit, Royal Devon University Healthcare NHS Foundation Trust, Exeter EX2 5DW, UK"},{"name":"Faculty of Health and Life Science, University of Exeter Medical School, Exeter EX1 2HZ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0545-9764","authenticated-orcid":false,"given":"Ma\u0142gorzata","family":"Woronkowicz","sequence":"additional","affiliation":[{"name":"North Devon District Hospital, Royal Devon University Healthcare NHS Foundation Trust, Barnstaple EX31 4JB, UK"},{"name":"Moorfields Eye Hospital NHS Foundation Trust, London EC1V 2PD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Skopi\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, SPKSO Ophthalmic University Hospital, Medical University of Warsaw, 00-576 Warsaw, Poland"},{"name":"Department of Histology and Embryology, Medical University of Warsaw, 02-004 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Britten-Jones, A.C., Wang, M.T.M., Samuels, I., Jennings, C., Stapleton, F., and Craig, J.P. 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