TIGIT-Fc Prolongs Corneal Allograft Survival in Mice by Upregulating TIGIT/CD226 Expression and the Proportion of Helios+Foxp3+ Treg Cells
TIGIT-Fc Prolongs Corneal Allograft Survival in Mice by Upregulating TIGIT/CD226 Expression and the Proportion of Helios+Foxp3+ Treg Cells
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TIGIT-Fc 通过上调 TIGIT/CD226 表达和 Helios Foxp3 Treg 细胞的比例来延长小鼠角膜同种异体移植物的存活
DOI：
10.1097/tp.0000000000004257
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发表时间：
2023-02-01
期刊：
影响因子：
6.2
通讯作者：
Jie，Ying
中科院分区：
文献类型：
--
作者：
Li，Shang;Zhang，Peng;Jie，Ying
背景：减少移植物排斥反应仍然是角膜移植术后支持移植物长期保留的关键问题。Treg在减少角膜移植排斥反应中的相关性已得到证实。最近有报道，除了Foxp 3，Helios也被认为是活化Treg的标志物。Helios+ Foxp 3 + Treg被认为是真正的免疫抑制性Treg。TIGIT是一种免疫抑制共刺激分子，发现其在Helios+ Foxp 3 + Treg的表面上高度表达。我们的目的是探索补充TIGIT是否会导致Helios+ Foxp 3 + Treg的扩增和活化，从而通过在鼠模型中局部和全身施用TIGIT-Fc治疗来介导角膜移植后的免疫耐受。与对照组相比，Fc治疗显著提高了角膜移植物的存活率。TIGIT-Fc处理增加TIGIT/CD 226表达、Helios+ Foxp 3 + Treg细胞的比例和增强的来自外周淋巴结分离的Treg细胞的离体抑制作用。结论：TIGIT-Fc治疗可通过TIGIT/CD 226-CD 155途径特异性上调同种异体角膜移植后Helios+ Foxp 3 + Treg介导的免疫应答，提高同种异体角膜移植物的存活率。
Background.Reduction of graft rejection remains key issue for supporting long-term graft retention after corneal transplantation. The relevance of Treg in reduction of corneal allografts rejection has been demonstrated. It has been recently reported that in addition to Foxp3, Helios is also considered to be a marker of activated Treg. Helios+ Foxp3+ Treg are considered to be the true immunosuppressive Treg. TIGIT is an immunosuppressive costimulatory molecule that was found to be highly expressed on the surface of Helios+ Foxp3+ Treg.Methods.In this study, we aimed to explore whether supplementing TIGIT would result in an expansion and activation of Helios+ Foxp3+ Treg thus to mediate an immune tolerance following corneal transplantation by administering topically and systemically TIGIT-Fc treatment in murine models.Results.TIGIT-Fc treatment significantly improved the survival of corneal allograft compared with the control group. TIGIT-Fc treatment increased TIGIT/CD226 expression, the proportion of Helios+ Foxp3+ Treg cells and an enhanced ex vivo suppressive effect from peripheral lymph nodes isolated Treg cells. Furthermore, the expression of Helios in corneal grafts was upregulated, whereas expression of CD226 and production of aqueous interferon-γ and VEGF were reduced by TIGIT-Fc treatment.Conclusions.TIGIT-Fc treatment could specifically upregulate Helios+ Foxp3+ Treg-mediated immune response after allogeneic corneal transplantation via TIGIT/CD226-CD155 pathway which improves the survival of allografts.