研究动态
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传统的I型迁移性CD103+树突状细胞对角膜移植物存活至关重要。

Conventional Type I Migratory CD103+ Dendritic Cells are Required for Corneal Allograft Survival.

发表日期:2023 Jan 12
作者: Tomas Blanco, Rohan Bir Singh, Hayate Nakagawa, Yukako Taketani, Thomas H Dohlman, Yihe Chen, Sunil K Chauhan, Jia Yin, Reza Danan
来源: Mucosal Immunology

摘要:

角膜移植排斥主要是由于宿主的T辅助细胞1(Th1)效应细胞介导的免疫反应对异基因组织的攻击。证据表明1型迁移性传统CD103 + 树突状细胞(CD103 + DC1)在肿瘤环境中获得免疫抑制表型;然而,在组织移植中,CD103 + DC1的参与仍然是一个重要的临床问题。在本研究中,我们评估了CD103 + DC1在抑制移植角膜异种移植免疫反应中的作用。CD103 + DC1的免疫抑制功能已在非移植环境中广泛研究。我们发现宿主CD103 + DC1浸润到角膜移植物,并迁移到引流淋巴结(DLN)通过程序性死亡配体1(PD-L1/PD-1)轴来抑制异基因性CD4 + Th1细胞。对CD103 + DC1的全身清除导致移植物受体中Th1活化增强,Treg功能受损,以及移植物排斥频率的增加。而移植物受体Rag1空小鼠重构的天然CD4 + CD25- T细胞可以有效产生外周Treg细胞(pTreg),但缺乏CD103 + DC1的小鼠则无法产生pTreg。此外,注射pTreg失效以拯救受到CD103 + DC1清除的接受者移植物的排斥反应。这些数据证明了CD103 + DC1在调节宿主异体免疫反应中的关键作用。简称:CD103 + DC在角膜异基因移植物中的作用。版权所有©2023作者。由Elsevier Inc.发表,保留所有权利。
Corneal transplant rejection primarily occurs due to T helper 1 (Th1) effector cell mediated immune response of the host toward allogeneic tissue. The evidence suggests that Type 1 migratory conventional CD103+ dendritic cells (CD103+DC1) acquire an immunosuppressive phenotype in the tumor environment; however, the involvement of CD103+DC1 in allograft survival continues to be an elusive question of great clinical significance in tissue transplantation. In this study, we assess the role of CD103+DC1 in suppressing Th1 alloreactivity against transplanted corneal allografts. The immunosuppressive function of CD103+DC1 has been extensively studied in non-transplantation settings. We found that host CD103+DC1 infiltrate the corneal graft and migrate to the draining lymph nodes (DLN) to suppress alloreactive CD4+ Th1 cells via the programmed death-ligand 1 (PD-L1/ PD-1) axis. The systemic depletion of CD103+ DC1 in allograft recipients leads to amplified Th1 activation, impaired Treg function, and increased frequency of allograft rejection. While allograft recipient Rag1 null mice reconstituted with naïve CD4+CD25- T cells efficiently generated peripheral Treg cells (pTreg), the CD103+DC1-depleted mice failed to generate pTreg. Furthermore, adoptive transfer of pTreg failed to rescue allografts in CD103+DC1-depleted recipients from rejection. These data demonstrate the critical role of CD103+DC1 in regulating host alloimmune responses. Short title: Role of CD103+ DCs in corneal allograft survival.Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.