Immune Regulatory Role of Parasympathetic Nervous System in Murine Corneal Allografts via Inhibition of Dendritic Cell Activation and T Cell Polarization

Abstract

PURPOSE. This study aimed to investigate the role of the parasympathetic nervous system in the allorecognition and rejection of murine corneal allografts. METHODS. We used 8- to 12-week-old male C57BL/6 (B6 and 1Ab) and BALB/C (IAd) murine models of corneal allografts. Following keratoplasty, graft survival rate and opacity were assessed for 5 weeks with or without the administration of a 0.1 mL scopolamine injection. Transcriptome changes and the presence of infiltrating antigen-presenting cells (APCs) and specific T-cell types were serially determined from the donor corneal button and draining lymph nodes (LNs) until 5 weeks after the keratoplasty procedure. RESULTS. Compared with the syngeneic models, the alloimmune models were observed to have significantly distinct gene expression profiles following keratoplasty. The total number of differentially expressed genes (DEGs; defined as ≥2-fold change) in the alloaccepted (allo-ac) models relative to the syngeneic ones was 1046 (712 upregulated and 334 downregulated), whereas 148 DEGs (136 upregulated and 12 downregulated) were identified when the Allo-ac models were compared to the allo-rejected (allo-rj) ones. Corneal opacity and rejection rates increased significantly after scopolamine injection. Flow analysis revealed significantly increased CD11b+, CD11c+, and F4/80+ cell infiltration in the donor cornea following the scopolamine treatment. Additionally, reduced Foxp3+ regulatory T (Treg) generation and enhanced Th1/Th17 polarization in the draining LNs were found in the scopolamine-treated allograft. CONCLUSIONS. Parasympathetic innervation may play a critical role in regulating corneal allograft survival by modulating APC activation, reducing Foxp3+ Treg generation, and enhancing Th1/Th17 polarization. Copyright 2026 The Authors.