Tocilizumab promotes corneal allograft survival in rats by modulating Treg-Th17 balance
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Jing Wu. Department of Huiqiao Building, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China. wujingsci@126.com; Ming Ma. Department of Ophthalmology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China. maming658587@163.com

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Supported by Science and Technology Planning Project of Guangdong Province (No.2017A020211005); Science and Technology Programme of Guangzhou, China 2016 (No.201607010386).

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    Abstract:

    AIM: To examine the therapeutic effects of tocilizumab on experimental corneal transplantation and its effect on Treg/Th17 balance. METHODS: Allograft corneal graft was performed between host Sprague Dawley and Wistar donor rats. The rats were randomly divided into four groups: normal, autograft, allograft, and allograft treated with tocilizumab. Kaplan-Meier was performed to draw the survival curve. The protein levels of interleukin-17A (IL-17A), vascular endothelial growth factor (VEGF), and forkhead box protein 3 (Foxp3) were measured by immunohistochemistry. The mRNA levels of IL-17A, VEGF, retinoid-related orphan receptor gammat (RORγt), interleukin-6 (IL-6) and Foxp3 were detected by reverse transcription real-time polymerase chain reaction (RT-PCR). The Treg and Th17 cells were investigated by flow cytometry. RESULTS: The survival time of tocilizumab group was (24±1.27d) longer than that of allograft group (10±0.55d). Moreover, immunohistochemical examination revealed that IL-17A and VEGF protein levels in the allograft group were significantly higher than that of tocilizumab group (P<0.01), while Foxp3 levels in the allograft group was significantly lower than that of the tocilizumab treated group (P<0.001). Flow cytometry showed that the number of Th17 cells in allograft group was significantly higher than that in tocilizumab group (P<0.001). Meanwhile, the number of Tregs was significantly lower than in tocilizumab group (P<0.001). Simultaneously, Foxp3 mRNA expression level in corneal tissues of tocilizumab treated group was significantly higher than other groups (P<0.001). CONCLUSION: These findings suggest that tocilizumab may promote corneal allograft survival, possibly by modulating Treg-Th17 balance.

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Wu XS, Lu XL, Wu J, Ma M, Yu J, Zhang ZY. Tocilizumab promotes corneal allograft survival in rats by modulating Treg-Th17 balance. Int J Ophthalmol 2019;12(12):1823-1831

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Publication History
  • Received:February 01,2019
  • Revised:June 27,2019
  • Adopted:
  • Online: November 06,2019
  • Published: