趋化因子诱饵受体 D6 模拟陷阱（D6MT）可预防小鼠角膜同种异体移植模型中的同种致敏和免疫排斥反应。

Chemokine decoy receptor D6 mimicking trap (D6MT) prevents allosensitization and immune rejection in murine corneal allograft model.

机构信息

*Institute of Vision Research, Department of Ophthalmology, and Corneal Dystrophy Research Institute, Yonsei University College of Medicine, Seoul, Korea; Kentucky Lions Eye Center, Department of Ophthalmology, University of Louisville, Louisville, Kentucky, USA; Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts, USA; Department of Anatomy and Cell Biology, University of Ulsan College of Medicine, Seoul, Korea; and Myunggok Eye Research Institute, Kim's Eye Hospital, Konyang University College of Medicine, Seoul, Korea.

出版信息

J Leukoc Biol. 2015 Feb;97(2):413-24. doi: 10.1189/jlb.5A0414-233RR. Epub 2014 Nov 13.

DOI:10.1189/jlb.5A0414-233RR

PMID:25395300

Abstract

Although corneal allotransplantation is performed in the immune-privileged cornea, many grafts are still rejected after transplantation. This study examined the role of chemokine receptor D6 expression in a corneal allograft rejection, investigated the modulation of D6 expression in cells, and determined the effect of D6 on graft survival. Interestingly, D6 was highly expressed in CD45 -: cells and the corneal epithelium of accepted corneal allografts. From the mouse corneal allograft model, TGF-β was found to play a key role in D6 up-regulation, leading to reduced CCL2, CCL5, and CCL3. To modulate D6 chemokine binding, a D6MT was developed and showed effective chemokine trapping through SPR and FACS assays. By treating corneal allografts with D6MT, the allograft survival rate was improved, and (lymph) angiogenesis was reduced. Direct allosensitization and DC LN homing was drastically reduced in the mouse corneal allograft model. These findings suggest that TGF-β is a positive regulator of D6 expression, and it is a potential therapeutic target to enhance the survival of corneal allografts.

摘要

尽管角膜同种异体移植是在免疫特惠的角膜中进行的，但许多移植物在移植后仍被排斥。本研究检查了趋化因子受体 D6 表达在角膜同种异体移植排斥中的作用，研究了细胞中 D6 表达的调节，并确定了 D6 对移植物存活的影响。有趣的是，D6 在 CD45 -：细胞和接受的角膜同种异体移植物的角膜上皮中高度表达。从小鼠角膜同种异体移植模型中发现，TGF-β 在 D6 的上调中起关键作用，导致 CCL2、CCL5 和 CCL3 的减少。为了调节 D6 趋化因子结合，开发了 D6MT，并通过 SPR 和 FACS 分析显示出有效的趋化因子捕获。通过用 D6MT 处理角膜同种异体移植物，提高了移植物的存活率，并减少了（淋）血管生成。在小鼠角膜同种异体移植模型中，直接同种致敏和 DC LN 归巢明显减少。这些发现表明，TGF-β 是 D6 表达的正调节剂，是增强角膜同种异体移植物存活的潜在治疗靶点。