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Dendritic Cells Transduced with Single Immunoglobulin IL-1-Related Receptor Exhibit Immature Properties and Prolong Islet Allograft Survival

机译:单个免疫球蛋白IL-1相关受体转导的树突状细胞具有不成熟的特性并能延长胰岛同种异体移植的存活时间。

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摘要

Members of toll-like receptor-interleukin 1 receptor signaling [TLR/IL-1R (TIR)] superfamily mediate maturation of dendritic cells (DCs) and launch immune response in transplanted organs. In this study, we hypothesized that TIR8, also known as single immunoglobulin IL-1-related receptor (SIGIRR) molecule, refrain DCs from maturation and induce immune tolerance of transplanted organ. DCs were transduced with the recombinant adenovirus Ad5F35 to highly express SIGIRR (DC-SIGIRR), then injected to murine recipient before islet transplantation. It revealed that DCs transduced with SIGIRR had low expression of major histocompatibility and costimulatory molecules along with strong phagocytic ability in vitro assay. The data demonstrated that recipients treated with DC-SIGIRR had satisfying islet allograft function and long survival times, with an increase of Treg and reduction of Th17 in both spleen and draining lymph nodes in vivo. Therefore, genetic modification of SIGIRR inhibits DC activation and maturation, affects differentiation of T cell subsets, protects allograft biological function, and prolongs graft survival.
机译:Toll样受体-白介素1受体信号转导[TLR / IL-1R(TIR)]的成员介导树突状细胞(DC)的成熟并在移植的器官中发起免疫反应。在这项研究中,我们假设TIR8,也称为单免疫球蛋白IL-1相关受体(SIGIRR)分子,可阻止DC成熟并诱导移植器官的免疫耐受。用重组腺病毒Ad5F35转导DC以高表达SIGIRR(DC-SIGIRR),然后在胰岛移植之前将其注射到鼠受体中。结果表明,用SIGIRR转导的DC在体外测定中主要组织相容性和共刺激分子表达低,并且具有较强的吞噬能力。数据表明,接受DC-SIGIRR治疗的受体具有令人满意的胰岛同种异体移植功能和较长的存活时间,体内脾脏和引流淋巴结的Treg升高且Th17降低。因此,SIGIRR的基因修饰可抑制DC激活和成熟,影响T细胞亚群的分化,保护同种异体移植物的生物学功能,并延长移植物的存活时间。

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