Engineering an "infectious" T(reg) biomimetic through chemoselective tethering of TGF-β1 to PEG brush surfaces.
Engineering an "infectious" T(reg) biomimetic through chemoselective tethering of TGF-β1 to PEG brush surfaces.
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通过 TGF-β1 与 PEG 刷表面的化学选择性束缚来设计“感染性”T(reg) 仿生体。
DOI：
10.1016/j.biomaterials.2015.07.009
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发表时间：
2015
期刊：
影响因子：
14
通讯作者：
Stabler,CL
中科院分区：
文献类型：
--
作者：
Yang,EY;Kronenfeld,JP;Gattás-Asfura,KM;Bayer,AL;Stabler,CL
移植后对同种异体移植物的免疫反应的调节对于改善移植物的结果和持续时间至关重要。在许多方法中，利用调节性T细胞（Treg）诱导的显性耐受性具有巨大的前景。最近的研究强调了细胞表面结合的TGF-β1对Treg促进感染耐受性的独特功效，即赋予一个细胞对另一个细胞的抑制能力。为了模拟该特征，使用Staudinger连接将TGF-β1化学选择性地栓系到惰性和活性聚合物移植平台。我们报告了这些工程化TGF-β1表面的合成和功能表征。与TGF-β1相连的惰性珠子能够有效地将幼稚CD 4 + CD 62 LhiT细胞转化为功能性Treg。一致地，从惰性表面到活细胞的缀合方案的翻译也导致功能性Treg的有效产生。此外，证明了这些平台产生抗原特异性Treg的能力。这些发现说明栓系的TGF-β1生物材料平台作为“感染性”Tregand发挥作用的独特能力，为同种异体移植产生致耐受性微环境提供了令人信服的方法。
Modulation of immunological responses to allografts following transplantation is of pivotal importance to improving graft outcome and duration. Of the many approaches, harnessing the dominant tolerance induced by regulatory T cells (Treg) holds tremendous promise. Recent studies have highlighted the unique potency of cell surface-bound TGF-β1 on Tregfor promoting infectious tolerance, i.e. to confer suppressive capacity from one cell to another. To mimic this characteristic, TGF-β1 was chemoselectively tethered to inert and viable polymer grafting platforms using Staudinger ligation. We report the synthesis and functional characterization of these engineered TGF-β1 surfaces. Inert beads tethered with TGF-β1 were capable of efficiently converting naïve CD4+CD62LhiT cells to functional Treg. Concordantly, translation of conjugation scheme from inert surfaces to viable cells also led to efficient generation of functional Treg. Further, the capacity of these platforms to generate antigen-specific Tregwas demonstrated. These findings illustrate the unique faculty of tethered TGF-β1 biomaterial platforms to function as an “infectious” Tregand provide a compelling approach for generating tolerogenic microenvironments for allograft transplantation.