The cornea is classically regarded as an immune-privileged tissue. However, recent studies have identified T cells in the healthy human cornea that are absent in specific pathogen-free (SPF) mice. The identity of these T cells, the systemic cues that drive their establishment, and the molecular mechanisms governing their corneal homing remain unknown. Here, we combine multimodal human data with tractable murine models to characterize the cellular basis of corneal immune surveillance. Immunofluorescence staining and confocal imaging of clinically non-inflamed human donor tissues revealed CD3⁺ T cells within the corneal epithelium. Flow cytometry revealed that these cells were predominantly CD8⁺, with a tissue-resident memory T (TRM) cell phenotype. In vivo confocal microscopy demonstrated that corneal T cell abundance increased with age, particularly in males, suggesting that accumulation is shaped by cumulative systemic immune experience. Whereas young SPF mice were devoid of corneal T cells, infection with pathogens that do not typically target the cornea induced long-lived TRM-like CD8⁺ T cells in the cornea. We identified CXCR6 as required for efficient T cell recruitment to the cornea of viral-infected mice. Together, our human and murine data support a model in which systemic immune history, age and biological sex influence local immune surveillance at the human ocular surface.
Mengliang Wu, Sarah C. Monard, Marina H. Yakou et al.· bioRxiv· 0 citations
Multiple clinical and translational studies have shown that infiltration of tumour-associated neutrophils is associated with advanced disease stages, increased metastatic spread, therapeutic resistance, and poorer overall survival across various cancer types. Beyond their traditional role as first responders to tissue damage and pathogen infection, neutrophils within the tumour microenvironment (TME) display remarkable functional plasticity, adopting phenotypes that can promote angiogenesis, extracellular matrix remodelling, immune suppression, and tumour cell invasion. Importantly, it is now recognised that the prognostic impact of neutrophils is highly context-dependent, shaped by tumour type, stage, and the evolving inflammatory milieu. Intravital imaging studies have revealed dynamic neutrophil behaviours, including distinct migratory patterns between intra-tumoural and peri-tumoural regions, interactions with tumour and immune cells, and contributions to processes such as metastasis and immune suppression. However, there is a lack of understanding of how transcriptionally defined neutrophil subsets translate into specific functional and behavioural states in the TME in vivo. This mini-review spotlights intravital imaging approaches that illuminate neutrophil dynamics in tumours. We also discuss how extrinsic regulators, including cancer-associated fibroblasts and neural inputs, direct neutrophil dynamics, further contributing to TME complexity.
Sapna Devi· Myeloid Cells· 0 citations
We use cookies to run the site and, with your consent, for analytics and to show ads.
See our Cookie Policy.
