Cutting edge:: Trans-signaling via the soluble IL-6R abrogates the induction of FoxP3 in naive CD4+ CD25- T cells
Cutting edge:: Trans-signaling via the soluble IL-6R abrogates the induction of FoxP3 in naive CD4+ CD25- T cells
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DOI：
10.4049/jimmunol.179.4.2041
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发表时间：
2007-08-15
影响因子：
4.4
通讯作者：
Becker, Christoph
中科院分区：
文献类型：
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作者：
Dominitzki, Sabine;Fantini, Massimo C.;Becker, Christoph
当调节性t细胞（Tregs）不能控制耐受性和免疫力之间的平衡时，慢性炎症性疾病可能会发生。或者，激活的免疫细胞可能会阻止这些疾病中treg的诱导或激活。在这项研究中，我们证明了通过可溶性IL-6受体进入T细胞的反式信号传导完全消除了适应性Tregs的从头诱导。在机制上，I -6反式信号传导增强了tgf - β信号传导抑制剂SJVL4D7的表达。因此，使用新创建的转基因小鼠，SMAD7在T细胞中的过表达使CD4(+) CD25(-) T细胞对ToxP3的诱导产生抗性。最后，在小鼠结肠炎模型中，IL-6反式信号传导抑制treg介导的抑制。综上所述，IL-6反式信号传导进入T细胞是阻断适应性Tregs发育的关键途径，因此可能在慢性炎症和自身免疫性疾病中改变效应T细胞和调节性T细胞数量之间的平衡中发挥关键作用。
Chronic inflammatory diseases may develop when reguZatory Tcells (Tregs)fail to control the balance between tolerance and immunity. Alternatively, activated immune cells might prevent the induction or activation of Tregs in such diseases. In this study, we demonstrate that trans-signaling into T cells via the soluble IL-6 receptor completely abrogates the de novo induction of adaptive Tregs. Mechanistically, I -6trans-signaling augmented the expression of the TGF-beta signaling inhibitor SJVL4D7.- Consequently, SMAD7 overexpression in T cells using newly created transgenic mice rendered CD4(+) CD25(-) T cells resistant to the induction of ToxP3. Finally, IL-6 trans-signaling inhibited Treg-mediated suppression in a murine model Of colitis. In summary, IL-6 trans-signaling into T cells emerges as a key pathway for blockade of the development of adaptive Tregs and thus may play a pivotal role in shifting the balance between effector and regulatory T cell numbers in chronic inflammatory and autoimmune diseases.