GATA3 controls Foxp3+ regulatory T cell fate during inflammation in mice
GATA3 controls Foxp3+ regulatory T cell fate during inflammation in mice
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DOI：
10.1172/jci57456
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发表时间：
2011-11-01
影响因子：
15.9
通讯作者：
Belkaid, Yasmine
中科院分区：
文献类型：
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作者：
Wohlfert, Elizabeth A.;Grainger, John R.;Belkaid, Yasmine
Tregs 不仅可以控制针对自身抗原的免疫反应，还可以抑制针对病原体和共生微生物群的免疫反应。 Tregs 对外周免疫稳态的控制依赖于它们在发炎部位积聚并适当适应局部环境的能力。迄今为止，人们对于控制 Treg 生理学这些方面的因素仍然知之甚少。在这里，我们发现经典的 Th2 转录因子 GATA3 在位于胃肠道和皮肤等屏障部位的 Tregs 中选择性表达。 TCR 和 IL-2 刺激后，小鼠和人类 Tregs 中的 GATA3 表达均被诱导。尽管 GATA3 不需要维持 Treg 稳态和稳态功能，但 GATA3 在炎症期间的 Treg 生理学中发挥着重要作用。事实上，Tregs 内在表达 GATA3 是其在炎症部位积聚并在各种极化或炎症环境中维持高水平 Foxp3 表达的能力所必需的。此外，我们的数据表明，GATA3 限制了 Treg 向效应 T 细胞表型的极化以及炎症组织中效应细胞因子的获取。总的来说，我们的工作揭示了我们认为 GATA3 在 T 细胞中复杂作用的一个新方面，并强调了炎症过程中控制 Treg 生理学的基本作用。
Tregs not only keep immune responses to autoantigens in check, but also restrain those directed toward pathogens and the commensal microbiota. Control of peripheral immune homeostasis by Tregs relies on their capacity to accumulate at inflamed sites and appropriately adapt to their local environment. To date, the factors involved in the control of these aspects of Treg physiology remain poorly understood. Here, we show that the canonical Th2 transcription factor GATA3 is selectively expressed in Tregs residing in barrier sites including the gastrointestinal tract and the skin. GATA3 expression in both murine and human Tregs was induced upon TCR and IL-2 stimulation. Although GATA3 was not required to sustain Treg homeostasis and function at steady state, GATA3 played a cardinal role in Treg physiology during inflammation. Indeed, the intrinsic expression of GATA3 by Tregs was required for their ability to accumulate at inflamed sites and to maintain high levels of Foxp3 expression in various polarized or inflammatory settings. Furthermore, our data indicate that GATA3 limits Treg polarization toward an effector T cell phenotype and acquisition of effector cytokines in inflamed tissues. Overall, our work reveals what we believe to be a new facet in the complex role of GATA3 in T cells and highlights what may be a fundamental role in controlling Treg physiology during inflammation.