Induced Regulatory T Cells Superimpose Their Suppressive Capacity with Effector T Cells in Lymph Nodes via Antigen-Specific S1p1-Dependent Egress Blockage.
Induced Regulatory T Cells Superimpose Their Suppressive Capacity with Effector T Cells in Lymph Nodes via Antigen-Specific S1p1-Dependent Egress Blockage.
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DOI：
10.3389/fimmu.2017.00663
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发表时间：
2017
影响因子：
7.3
通讯作者：
Wang B
中科院分区：
文献类型：
--
作者：
Geng S;Zhong Y;Zhou X;Zhao G;Xie X;Pei Y;Liu H;Zhang H;Shi Y;Wang B
调节性T细胞（Tcells）限制过度兴奋的淋巴细胞活化。虽然TcB与其抑制靶点之间的紧密接近对于最佳抑制是重要的，并且文献表明引流淋巴结（LN）可以作为抑制的主要位置，但是协调该事件的信号传导细节尚未完全表征。使用一个协议，使外周产生的诱导型抗原特异性T细胞（asTclase），以控制过敏原诱导的哮喘，我们已经确定了一个抗原特异性的机制，锁定asTclase在肺门淋巴结，这反过来又抑制气道炎症。在LN中抗原刺激后，抑制性asTl 4下调鞘氨醇-1-磷酸受体1出口受体表达。这些asT细胞反过来介导传入效应T细胞上相同受体的下调。因此，asT细胞和效应T细胞被锁定在这些引流淋巴结中，以延长相互作用。破坏这一保留序列的各个步骤可以消除由asTactinase控制的炎症。总的来说，这项研究确定了空间聚集的新要求，其抑制目标对asTreg功能至关重要，并通过Treg交通控制提出了治疗方案。
Regulatory T cells (Tregs) restrict overexuberant lymphocyte activation. While close proximity between Tregs and their suppression targets is important for optimal inhibition, and literature indicates that draining lymph nodes (LNs) may serve as a prime location for the suppression, signaling details orchestrating this event are not fully characterized. Using a protocol to enable peripheral generation of inducible antigen-specific Tregs (asTregs) to control allergen-induced asthma, we have identified an antigen-specific mechanism that locks asTregs within hilar LNs which in turn suppresses airway inflammation. The suppressive asTregs, upon antigen stimulation in the LN, downregulate sphingosine-1-phosphate receptor 1 egress receptor expression. These asTregs in turn mediate the downregulation of the same receptor on incoming effector T cells. Therefore, asTregs and effector T cells are locked in these draining LNs for prolonged interactions. Disruption of individual steps of this retention sequence abolishes the inflammation controlled by asTregs. Collectively, this study identifies a new requirement of spatial congregation with their suppression targets essential for asTreg functions and suggests therapeutic programs via Treg traffic control.