Dendritic Cells Coordinate the Development and Homeostasis of Organ-Specific Regulatory T Cells.
Dendritic Cells Coordinate the Development and Homeostasis of Organ-Specific Regulatory T Cells.
复制标题
DOI：
10.1016/j.immuni.2016.01.025
复制
发表时间：
2016-04-19
期刊：
影响因子：
32.4
通讯作者：
Savage PA
中科院分区：
文献类型：
--
作者：
Leventhal DS;Gilmore DC;Berger JM;Nishi S;Lee V;Malchow S;Kline DE;Kline J;Vander Griend DJ;Huang H;Socci ND;Savage PA
尽管由T细胞受体（TCR）介导的抗原识别影响Foxp3+调节性T（Treg）细胞生物学的许多方面，包括发育和功能，但体内将抗原呈递给Treg细胞的细胞类型在很大程度上仍不确定。通过追踪小鼠中Aire依赖性、前列腺特异性Treg细胞的克隆群体，我们证明了树突状细胞（DC）在调节器官特异性Treg细胞生物学中的重要作用。我们已经表明，胸腺发育的前列腺特异性Treg细胞需要抗原呈递的DC。此外，Batf3依赖性CD8α+ DCs被用于该克隆型的开发，并且对多克隆Treg细胞库的影响可以忽略不计。在外周，CCR7依赖性迁移DC协调前列腺引流淋巴结中器官特异性Treg细胞的激活。我们的研究结果表明，器官特异性Treg细胞的发育和外周调节依赖于DC的抗原呈递，暗示DC是器官特异性免疫耐受的关键介质。
Whereas antigen recognition mediated by the T cell receptor (TCR) influences many facets of Foxp3+ regulatory T (Treg) cell biology, including development and function, the cell types that present antigen to Treg cells in vivo remain largely undefined. By tracking a clonal population of Aire-dependent, prostate-specific Treg cells in mice, we demonstrated an essential role for dendritic cells (DCs) in regulating organ-specific Treg cell biology. We have shown that the thymic development of prostate-specific Treg cells required antigen presentation by DCs. Moreover, Batf3-dependent CD8α+ DCs were dispensable for the development of this clonotype and had negligible impact on the polyclonal Treg cell repertoire. In the periphery, CCR7-dependent migratory DCs coordinated the activation of organ-specific Treg cells in the prostate-draining lymph nodes. Our results demonstrate that the development and peripheral regulation of organ-specific Treg cells are dependent on antigen presentation by DCs, implicating DCs as key mediators of organ-specific immune tolerance.