Department of Biophysics, College of Basic Medical Sciences, Second Military Medical University, Shanghai 200433, China; Team SMMU-China of International Genetically Engineered Machine (iGEM) competitions, Department of Biophysics, Second Military Medical University, Shanghai 200433, China.
Department of Emergency Medicine, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
Clin Immunol. 2019 Jun;203:72-80. doi: 10.1016/j.clim.2019.04.007. Epub 2019 Apr 18.
The TIGIT (T cell immunoreceptor with Ig and ITIM domains) protein is a co-inhibitory receptor that has been reported to suppress autoreactive T and B cells to trigger immunological tolerance. We generated a new recombinant protein by connecting the extracellular domain of murine TIGIT to the Fc region of the mouse immunoglobulin IgG2a. The fusion protein was then characterized. The results suggested that among mice with lupus that were treated with the TIGIT-Ig fusion protein, the onset of proteinuria was delayed, serum concentrations of autoantibodies, such as antinuclear antibodies, were reduced without a decrease in the total IgG concentrations, and the survival rate was significantly increased compared to those of the controls. In conclusion, TIGIT-Ig administration showed promising results for both the prevention and treatment of autoimmune diseases in mice. This indicates that treatment with recombinant human TIGIT-Ig shows promise as an effective way to treat human autoimmune diseases.
T 细胞免疫球蛋白和免疫受体酪氨酸抑制基序（T cell immunoreceptor with Ig and ITIM domains，TIGIT）蛋白是一种共抑制受体，据报道，它可抑制自身反应性 T 和 B 细胞，从而引发免疫耐受。我们通过将小鼠 TIGIT 的细胞外结构域与小鼠免疫球蛋白 IgG2a 的 Fc 区连接，生成了一种新的重组蛋白。然后对融合蛋白进行了表征。结果表明，与接受 TIGIT-Ig 融合蛋白治疗的狼疮小鼠相比，蛋白尿的发病时间延迟，血清自身抗体（如抗核抗体）浓度降低，而总 IgG 浓度没有下降，与对照组相比，存活率显著提高。总之，TIGIT-Ig 的给药在预防和治疗小鼠自身免疫性疾病方面显示出良好的效果。这表明，重组人 TIGIT-Ig 的治疗有希望成为治疗人类自身免疫性疾病的有效方法。
