Anti-IL-17 therapy restricts and reverses late-term corneal allorejection

The Journal of Immunology : Official Journal of the American Association of Immunologists
Xiao-Tang YinPatrick M Stuart

Abstract

Corneal allograft rejection has been described as a Th1-mediated process involving IFN-γ production. However, recent evidence also implicated IL-17 as being involved in acute corneal allograft responses. Our data support that IL-17 is involved in early acute corneal allograft acceptance. However, we decided to extend these studies to include a later phase of rejection in which there is a peak of IL-17 production that is >15-fold higher than that seen during acute rejection and occurs >45 d postengraftment at the onset of late-term rejection. We demonstrate that neutralizing IL-17A at this time significantly reduced corneal graft rejection. Surprisingly, when corneal grafts that are undergoing this later phase of rejection are treated with anti-IL-17A, there is a reversal of both opacity and neovascularization. Compared with the early phase of rejection, the cellular infiltrate is significantly less, with a greatly reduced presence of Gr-1(+) neutrophils and a relative increase in CD4(+) T cells and macrophages. We went on to identify that the cells expressing IL-17 were CD4(+) IL-17(+) T cells and, somewhat surprisingly, IL-17(+) F4/80(+) macrophages within the rejecting corneal allografts. Taken together, these findings descri...Continue Reading

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Citations

Jan 8, 2018·Cellular and Molecular Life Sciences : CMLS·Maryam TahvildariReza Dana
Mar 25, 2016·World Journal of Transplantation·Tian YuLucia Kuffová
Aug 4, 2018·Investigative Ophthalmology & Visual Science·Han WangMin Zhao
Jun 28, 2016·Nature Reviews. Nephrology·Qiuheng Zhang, Elaine F Reed
Oct 13, 2017·Cornea·Takenori InomataReza Dana
May 26, 2017·Ocular Immunology and Inflammation·Aihua Hou, Louis Tong

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