T-bet Regulates Natural Regulatory T Cell Afferent Lymphatic Migration and Suppressive Function.
T-bet Regulates Natural Regulatory T Cell Afferent Lymphatic Migration and Suppressive Function.
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DOI：
10.4049/jimmunol.1502537
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发表时间：
2016-03-15
期刊：
影响因子：
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通讯作者：
Bromberg JS
中科院分区：
文献类型：
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作者：
Xiong Y;Ahmad S;Iwami D;Brinkman CC;Bromberg JS
T-bet对于nTreg调节Th 1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−/−nTreg而不是iTreg未能像野生型Treg那样有效地延长移植物存活。T-bet−/− nTreg在体外没有功能缺陷，但未能像野生型那样有效地从移植物归巢到dLN。T-bet调节粘附和迁移相关分子的表达，影响nTreg在组织中的分布，因此T-bet−/− nTreg保留在移植物中，而不是迁移到粘附物和dLN中。相比之下，野生型和T-bet−/− CD 4 + Tconv和iTreg均正常向传入轴突迁移。T-bet−/− nTreg在移植物中表现出不稳定性，无法抑制抗原特异性CD 4 + T细胞并阻止其浸润到移植物和dLN中。因此，T-bet调节nTreg迁移到传入神经和dLN中，并因此调节其体内抑制稳定性。
T-bet is essential for 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 iTreg 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 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+ Tconv and iTreg migrated normally toward afferent lymphatics. T-bet−/− nTreg displayed instability in the graft, failing to suppress antigen-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.