Tocilizumab promotes corneal allograft survival in rats by modulating Treg-Th17 balance

作     者：Xiao-Song Wu Xiao-Li Lu Jing Wu Ming Ma Jian Yu Zhen-Yu Zhang 

作者机构：Dpartment of OphthalmologyNanfang HospitalSouthern Medical UniversityGuangzhou 510515Guangdong ProvinceChina Department of Huiqiao BuildingNanfang HospitalSouthern Medical UniversityGuangzhou 510515Guangdong ProvinceChina Guangdong Women And Children HospitalGuangzhou 511400Guangdong ProvinceChina 

出 版 物：《International Journal of Ophthalmology(English edition)》 (国际眼科杂志（英文版）)

年 卷 期：2019年第12卷第12期

页      面：1823-1831页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

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

主　　题：tocilizumab corneal transplantation Th17/Treg rats 

摘      要：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 protein3(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±1.27 d) longer than that of allograft group(10±0.55 d).Moreover, immunohistochemical examination revealed that IL-17A and VEGF protein levels in the allograft group were significantly higher than that of tocilizumab group(P0.01),while Foxp3 levels in the allograft group was significantly lower than that of the tocilizumab treated group(P0.001).Flow cytometry showed that the number of Th17 cellsin allograft group was significantly higher than that in tocilizumab group(P0.001). Meanwhile, the number of Tregs was significantly lower than in tocilizumab group(P0.001). Simultaneously, Foxp3 m RNA expression level in corneal tissues of tocilizumab treated group was significantly higher than other groups(P0.001). CONCLUSION: These findings suggest that tocilizumab may promote corneal allograft survival, possibly by modulating Treg-Th17 balance.