STAT6 controls the number of regulatory T cells in vivo, thereby regulating allergic lung inflammation.
STAT6 controls the number of regulatory T cells in vivo, thereby regulating allergic lung inflammation.
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DOI：
10.4049/jimmunol.1300486
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发表时间：
2013-08-15
期刊：
影响因子：
--
通讯作者：
Keegan AD
中科院分区：
文献类型：
--
作者：
Dorsey NJ;Chapoval SP;Smith EP;Skupsky J;Scott DW;Keegan AD
STAT6在IL-4介导的变态反应中起核心作用。一些研究表明，调节性T细胞(Treg)在体外可以受到IL-4的调节。我们之前的研究表明，即使提供野生型−/−效应器，STAT6Th2小鼠对过敏性肺部炎症也具有高度的抵抗力，并且它们增加了Treg的数量。然而，STAT6在体内调节Tregs在变态反应性肺部炎症中的作用还没有得到彻底的研究。为探讨Treg和STAT6在变态反应性炎症过程中的相互作用，对STAT6−/−、STAT6×RAG2Th2和RAG2Th2效应器过继转移后的卵清蛋白致敏和攻击进行了研究，并用抗CD2 5抗体(PC6 1)将Treg耗尽/灭活。正如预期的那样，STAT6−/−小鼠对呼吸道炎症和重塑具有高度的抵抗力。相比之下，用PC61治疗的STAT6−/−小鼠的变应性肺部炎症部分恢复到STAT6×RAG2−/−小鼠的水平。在某些情况下，STAT6×RAG2Th2型−/−小鼠也被给予自然(N)Tregs和Th2型效应器。过继转移nTregs可显著降低STAT6×RAG2−/−小鼠的BAL嗜酸性粒细胞组成，抑制T细胞向肺内的迁移和气道重塑，达到与STAT6−/−小鼠相当的水平。这些结果表明STAT6依赖的Tregs在体内被抑制以促进过敏性呼吸道炎症。
STAT6 plays a central role in IL-4-mediated allergic responses. Several studies indicate that regulatory T cells (Treg) can be modulated by IL-4 in vitro. We previously showed that STAT6−/− mice are highly resistant to allergic lung inflammation even when wild type Th2 effectors were provided and that they have increased numbers of Tregs. However, the role of STAT6 in modulating Tregs in vivo during allergic lung inflammation has not been thoroughly investigated. To investigate Treg and STAT6 interaction during allergic inflammation, STAT6−/−, STAT6×RAG2−/− and RAG2−/− mice were subjected to OVA sensitization and challenge following adoptive transfer of OVA-specific, wild type Th2 effectors with or without prior Treg depletion/ inactivation using anti-CD25 (PC61). As expected, STAT6−/− mice were highly resistant to airway inflammation and remodeling. In contrast, allergic lung inflammation was partially restored in STAT6−/− mice treated with PC61 to levels observed in STAT6×RAG2−/− mice. In some cases, STAT6×RAG2−/− mice were also given natural (n) Tregs along with Th2 effectors. Adoptive transfer of nTregs caused a substantial reduction in BAL eosinophil composition and suppressed airway remodeling and T cell migration into the lung in STAT6×RAG2−/− mice to levels comparable to those in STAT6−/− mice. These results demonstrate the STAT6-dependent suppression of Tregs in vivo in order to promote allergic airway inflammation.
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影响因子：
32.4
作者：
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发表时间：
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影响因子：
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作者：
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