Targeting Dendritic Cells: An Emerging Agent in Dry Eye Disease Management

Dry eye disease (DED), a multifactorial disorder characterized by tear film instability and ocular surface inflammation, remains a therapeutic challenge due to its complex immunopathogenesis. Emerging evidence highlights dendritic cells (DCs), including conventional (cDCs) and plasmacytoid subsets (pDCs), as pivotal mediators bridging innate and adaptive immune responses in DED. This review delineates the mechanisms by which DCs drive DED progression. Hyperosmolar stress, apoptotic debris, and goblet cell dysfunction activate DCs, promoting their migration to draining lymph nodes and subsequent priming of Th1/Th17 cells, which perpetuate lacrimal gland inflammation and ocular surface damage. Functional alterations in DCs that exacerbate neural-immune crosstalk include upregulated TLR7/9, STING, and S100A8/A9 pathways, and enhanced pro-inflammatory cytokine production including IL-12, IFN-I, and IL-23. Clinically, in vivo confocal microscopy reveals elevated corneal DCs density and activation, which correlate with symptom severity, tear break-up time, and corneal nerve abnormalities, underscoring their potential as diagnostic and prognostic biomarkers. Therapeutic strategies targeting DCs include reducing DCs density and activation (e.g. netrin-1, mesenchymal stem cell-derived extracellular vesicles), modulating inflammatory cytokine production (e.g. thrombospondin-1, mesenchymal stem cell, and butyrate), and regulating DCs-T cells interactions (e.g. neurokinin-1 antagonists, CD40/CD40L blockade), which offer novel avenues for immune regulation.