Exp Eye Res . 2016 Oct;151:134-41. doi: 10.1016/j.exer.2016.08.010. Epub 2016 Aug 25.

CD25 siRNA induces Treg/Th1 cytokine expression in rat corneal transplantation models

Qin Qin  1 Dan Luo  1 Yunjie Shi  1 Qingqing Zhao  1 Yuan Chen  1 Jing Wu  1 Min Zhao  2

Affiliations

  • 1 Department of Ophthalmology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Eye Bank, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing, China.
  • 2 Department of Ophthalmology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Eye Bank, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing, China. Electronic address: minzhaomz@outlook.com.

Abstract

Corneal graft rejection is the major reason for transplant failure. CD25 plays an important role in the induction of corneal graft rejection by regulating CD4(+) T cell function. Furthermore, CD25-mediated signaling is closely associated with the expression of Treg cytokines (IL-10, TGF-β) and Th1 cytokines (IFN-γ, IL-1β, and TNF-α). In the current study, corneal transplantation was performed on Wistar rats as donors and Sprague-Dawley rats as recipients. The survival curves indicated that CD25 siRNA treatment significantly prolonged graft survival time (mean survival time [MST], 14.8 ± 0.7 days) as compared with controls (MST, 7.6 ± 0.7 days; n = 12, p < 0.01). HE staining showed that CD25 siRNA alleviated inflammatory cell infiltration. At days 3, 7, 14, and 21, the mRNA and protein expression of CD25 in the CD25 siRNA groups were less than those of the control group, although the most significant decrease of CD25 protein was at day 3. The expression of IL-10 and TGF-β in the CD25 siRNA group increased, while IFN-γ, IL-1β, and TNF-α expression decreased, as well as no significant changes in Foxp3 expression were observed at day 14 post-operation. In conclusion, CD25 siRNA gene therapy played a protective role in corneal graft rejection via up-regulation of Treg cytokine expression and down-regulation of Th1 cytokine expression.

Keywords: CD25; CD25 siRNA treatment; Th1 cytokines; Treg cytokines.

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