Targeting of the hNC16A collagen domain to dendritic cells induces tolerance to human type XVII collagen
Targeting of the hNC16A collagen domain to dendritic cells induces tolerance to human type XVII collagen
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DOI：
10.1111/j.1600-0625.2012.01474.x
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发表时间：
2012-05-01
影响因子：
3.6
通讯作者：
Bauer, Johann W.
中科院分区：
文献类型：
--
作者：
Ettinger, Monika;Gratz, Iris K.;Bauer, Johann W.
特异于鼠DEC 205的抗体可用于将抗原靶向树突细胞。将人XVII型胶原蛋白的免疫显性结构域hNC 16 A与该抗体（DEC-hNC 16 A）融合，并通过基因枪转染作为表达质粒施用，目的是在皮肤移植模型中诱导对人XVII型胶原蛋白的耐受性。用DEC-hNC 16 A转染的小鼠用来自经工程改造以表达人XVII型胶原的转基因小鼠的皮肤移植物攻击。在用DEC-hNC 16 A处理后，移植物存活延长或移植物被无限接受（分别为33%和16%），而在未处理的对照中100%的移植物被排斥。移植物的接受与不存在CD 4+浸润和密集的CD 8 + T细胞浸润相关，并且不严格依赖于抗体产生。我们的研究结果表明，DEC-hNC 16 A靶向树突状细胞在体内导致转基因皮肤移植物的存活延长。这表明DEC 205靶向可用于诱导对皮肤抗原的耐受，这将增加大疱性表皮病患者皮肤基因治疗成功的机会。
Antibodies, specific to murine DEC205, can be used to target antigens to dendritic cells. The immunodominant domain of human type XVII collagen, hNC16A, was fused to this antibody (DEC-hNC16A) and was administered as expression plasmid by gene gun transfection with the aim of inducing tolerance to human type XVII collagen in a skin transplantation model. Mice transfected with DEC-hNC16A were challenged with skin grafts from transgenic mice engineered to express human type XVII collagen. Graft survival was either prolonged or grafts were accepted infinitely (33% and 16%, respectively) upon treatment with DEC-hNC16A while 100% of grafts were rejected in untreated controls. Graft acceptance was associated with the absence of a CD4+ infiltrate and a dense CD8+ T-cell infiltrate and was not strictly dependent on antibody production. Our results show that DEC-hNC16A targets dendritic cells in vivo leading to prolonged survival of transgenic skin grafts. This indicates that DEC205-targeting may be used for the induction of tolerance to skin antigens, which would increase the chances of successful skin gene therapy of epidermolysis bullosa patients.