Xue Zhicheng, Zhang Xuzhi, Chen Maogen, Lu Xinjun, Deng Ronghai, Ma Yi
Department of Organ Transplantation, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Front Immunol. 2017 Nov 30;8:1671. doi: 10.3389/fimmu.2017.01671. eCollection 2017.
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 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 . Therefore, genetic modification of SIGIRR inhibits DC activation and maturation, affects differentiation of T cell subsets, protects allograft biological function, and prolongs graft survival.
Toll样受体-白细胞介素1受体信号传导[TLR/IL-1R (TIR)]超家族成员介导树突状细胞(DCs)成熟并启动移植器官中的免疫反应。在本研究中，我们假设TIR8，也称为单免疫球蛋白IL-1相关受体(SIGIRR)分子，可抑制DCs成熟并诱导移植器官的免疫耐受。用重组腺病毒Ad5F35转导DCs以高表达SIGIRR(DC-SIGIRR)，然后在胰岛移植前注射到小鼠受体中。结果显示，经SIGIRR转导的DCs主要组织相容性和共刺激分子表达较低，吞噬能力检测显示吞噬能力较强。数据表明，接受DC-SIGIRR治疗的受体具有良好的胰岛同种异体移植功能和较长的存活时间，脾脏和引流淋巴结中的调节性T细胞增加，辅助性T细胞17减少。因此，SIGIRR的基因修饰可抑制DC激活和成熟，影响T细胞亚群分化，保护同种异体移植的生物学功能并延长移植物存活时间。
