CD98-induced CD147 signaling stabilizes the Foxp3 protein to maintain tissue homeostasis.
CD98-induced CD147 signaling stabilizes the Foxp3 protein to maintain tissue homeostasis.
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CD98 诱导的 CD147 信号传导稳定 Foxp3 蛋白以维持组织稳态。
DOI：
10.1038/s41423-021-00785-7
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发表时间：
2021-12
影响因子：
24.1
通讯作者：
Zhu P
中科院分区：
文献类型：
--
作者：
Geng J;Chen R;Yang FF;Lin P;Zhu YM;Fu X;Wang K;Feng Z;Wu J;Zhang H;Li QJ;Chen ZN;Zhu P
调节性T细胞（Treg）的稳定性对于适当控制免疫活性和组织稳态是必要的。然而，目前尚不清楚Treg稳定性是否必须持续增强或在生理条件下的发育过程中建立。Foxp 3已被表征为控制Treg稳定性的遗传程序的中心介体。在这里，我们证明，为了维持Foxp 3蛋白的表达，TcB需要细胞与细胞的接触，这是由CD 147-CD 98相互作用介导的。随着T细胞的产生，在其表面表达的CD 147受到在生理环境中广泛表达的CD 98的刺激。因此，CD 147的胞内结构域与CDK 2结合并将其保留在膜附近，导致Foxp 3去磷酸化并防止Foxp 3降解。此外，在病理和生理条件下，Foxp 3 + T细胞的最佳分布取决于CD 98的表达。因此，我们的研究提供了直接证据，即Foxp 3依赖性Treg稳定性通过周围环境中CD 147和CD 98之间的相互作用在外周中得到加强。更重要的是，高表达CD 147的TclD能有效抑制炎症反应，维持Foxp 3的稳定性，这对TclD在免疫治疗中的应用具有指导意义。
Regulatory T cell (Treg) stability is necessary for the proper control of immune activity and tissue homeostasis. However, it remains unclear whether Treg stability must be continually reinforced or is established during development under physiological conditions. Foxp3 has been characterized as a central mediator of the genetic program that governs Treg stability. Here, we demonstrate that to maintain Foxp3 protein expression, Tregs require cell-to-cell contact, which is mediated by the CD147-CD98 interaction. As Tregs are produced, CD147, which is expressed on their surface, is stimulated by CD98, which is widely expressed in the physiological environment. As a result, CD147’s intracellular domain binds to CDK2 and retains it near the membrane, leading to Foxp3 dephosphorylation and the prevention of Foxp3 degradation. In addition, the optimal distribution of Foxp3+ Tregs under both pathological and physiological conditions depends on CD98 expression. Thus, our study provides direct evidence that Foxp3-dependent Treg stability is reinforced in the periphery by the interaction between CD147 and CD98 in the surrounding environment. More importantly, Tregs with high CD147 expression effectively inhibit inflammatory responses and maintain Foxp3 stability, which has guiding significance for the application of Tregs in immunotherapy.
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影响因子：
24.1
作者：
Guo N;Ye S;Zhang K;Yu X;Cui H;Yang X;Lin P;Lv M;Miao J;Zhang Y;Han Q;Zhang R;Chen Z;Zhu P
通讯作者：
Zhu P
影响因子：
3.7
作者：
COPPOCK, DL;BUFFOLINO, P;NATHANSON, L
通讯作者：
NATHANSON, L
影响因子：
4.4
作者：
Gondek, DC;Lu, LF;Noelle, RJ
通讯作者：
Noelle, RJ
影响因子：
32.4
作者：
Grossman, WJ;Verbsky, JW;Ley, TJ
通讯作者：
Ley, TJ
影响因子：
30.5
作者：
Dominguez-Villar M;Hafler DA
通讯作者：
Hafler DA