Professor Yonsei Univ. Col. of Med., United States
Introduction/Rationale: 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, the graft survival rate and opacity were assessed until 12 weeks with or without the administration of a 0.1 mL scopolamine injection. Transcriptome changes, 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 8 weeks after the keratoplasty procedure.
Results: Compared to the syngeneic models, the alloimmune models were observed to have significantly distinct gene expression profiles following the 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, 334 downregulated), whereas 148 DEGs (136 upregulated, 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 the scopolamine injection. Although the CD207+ cells were not change, CD11c+ and F4/80+ cell traffic to the draining LNs increased significantly following the scopolamine treatment. Additionally, Foxp3+ Treg generation and enhanced Th1/Th17 polarization in the early stage grafts were found with scopolamine injection.
Conclusion: Parasympathetic innervation may play a critical role in terms of regulating corneal allograft survival by modulating APC activation, lymph node trafficking, and T-cell infiltration.
