T 细胞转录因子 T-bet 调控天然调节性 T 细胞的输入淋巴管迁移及抑制功能。
T-bet Regulates Natural Regulatory T Cell Afferent Lymphatic Migration and Suppressive Function.
作者信息
Xiong Yanbao, Ahmad Sarwat, Iwami Daiki, Brinkman C Colin, Bromberg Jonathan S
机构信息
Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD 21201;
Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD 21201; Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201; and.
出版信息
J Immunol. 2016 Mar 15;196(6):2526-40. doi: 10.4049/jimmunol.1502537. Epub 2016 Feb 15.
T-bet is essential for natural regulatory T cells (nTreg) to regulate Th1 inflammation, but whether T-bet controls other Treg functions after entering the inflammatory site is unknown. In an islet allograft model, T-bet(-/-) nTreg, but not induced Treg, failed to prolong graft survival as effectively as wild-type Treg. T-bet(-/-) nTreg had no functional deficiency in vitro but failed to home from the graft to draining lymph nodes (dLN) as efficiently as wild type. T-bet regulated expression of adhesion- and migration-related molecules, influencing nTreg distribution in tissues, so that T-bet(-/-) nTreg remained in the grafts rather than migrating to lymphatics and dLN. In contrast, both wild-type and T-bet(-/-) CD4(+) conventional T cells and induced Treg migrated normally toward afferent lymphatics. T-bet(-/-) nTreg displayed instability in the graft, failing to suppress Ag-specific CD4(+) T cells and prevent their infiltration into the graft and dLN. Thus, T-bet regulates nTreg migration into afferent lymphatics and dLN and consequently their suppressive stability in vivo.
T-bet对于天然调节性T细胞（nTreg）调节Th1炎症至关重要，但T-bet进入炎症部位后是否控制其他Treg功能尚不清楚。在胰岛同种异体移植模型中，T-bet基因敲除的nTreg，而非诱导性Treg，未能像野生型Treg那样有效地延长移植物存活时间。T-bet基因敲除的nTreg在体外没有功能缺陷，但从移植物归巢至引流淋巴结（dLN）的效率不如野生型。T-bet调节黏附及迁移相关分子的表达，影响nTreg在组织中的分布，使得T-bet基因敲除的nTreg留在移植物中，而不是迁移至淋巴管和dLN。相反，野生型和T-bet基因敲除的CD4⁺传统T细胞以及诱导性Treg均正常地向传入淋巴管迁移。T-bet基因敲除的nTreg在移植物中表现出不稳定性，无法抑制抗原特异性CD4⁺T细胞并阻止其浸润至移植物和dLN。因此，T-bet调节nTreg向传入淋巴管和dLN的迁移，进而调节其在体内的抑制稳定性。
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