Background: Cluster of differentiation 4 positive (CD4+) T cells play an important role in corneal graft rejection, especially the dynamic balance between regulatory T cells and helper T cells. This study aims to explore the upstream and downstream regulatory mechanisms of Th17 cell differentiation-mediated corneal allograft rejection.
Methods: By establishing rat corneal allograft transplantation model, transcriptome analysis was carried out to screen the differentially expressed genes related to T helper 17 (Th17) cell differentiation, and then cell experiments were used to verify the effect of miR-673-5p/Janus Kinase 2 (JAK2) signal on naïve CD4+ T cell differentiation and the proliferation, migration, and tube formation ability of human umbilical vein endothelial cells (HUVECs). Finally, the role of miR-673-5p/JAK2 signal in corneal allograft rejection was verified by animal model in vivo.
Results: The results showed that JAK2/STAT3 signaling activation-mediated Th17 cell differentiation was significantly up-regulated during corneal allograft rejection, and miR-673-5p expression was down-regulated after corneal allograft rejection. Low expression of miR-673-5p promoted Th17 cell differentiation by up-regulating JAK2, and then promoted placental growth factor (PLGF)mediated corneal neovascularization (CNV).
Conclusions: The results of this study suggested that low expression of miR-673-5p is a promoter of corneal allograft rejection. Overexpression of miR-673-5p can improve the survival rate of corneal allografts by inhibiting the differentiation and maturation of Th17 cells mediated by JAK2/STAT3 signaling.
Keywords: Corneal allograft rejection; JAK2; Th17 cell differentiation; corneal neovascularization (CNV); miR-673-5p.
2021 Annals of Translational Medicine. All rights reserved.