Parasympathetic neural regulation of immune tolerance in corneal allografts via inhibition of dendritic cell activation and T cell polarization 2253341

Abstract

Abstract Introduction 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. Funding Source This work was supported by the Advanced Science Research Program (Grant no. RS-2024-00344204) through the National Research Foundation of Korea (NRF), funded by the Ministry of Education, Science, and Technology, Seoul, Korea Topic Categories Transplantation Immunology (TRAN)