Mucosal Immunology Unit, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.
J Clin Invest. 2011 Nov;121(11):4503-15. doi: 10.1172/JCI57456. Epub 2011 Oct 3.
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.
调节性 T 细胞（Tregs）不仅能抑制自身抗原的免疫反应，还能抑制针对病原体和共生菌群的免疫反应。Tregs 通过其在炎症部位的积累能力，并适当适应其局部环境来控制外周免疫稳态。迄今为止，控制 Treg 生理学这些方面的因素仍知之甚少。在这里，我们表明，经典的 Th2 转录因子 GATA3 选择性地表达于屏障部位的 Tregs 中，包括胃肠道和皮肤。在 TCR 和 IL-2 刺激下，无论是在小鼠还是人类 Tregs 中均诱导 GATA3 表达。虽然 GATA3 对于 Treg 在稳态下的稳态和功能并不必需，但在炎症过程中，GATA3 在 Treg 生理学中起着重要作用。事实上，Tregs 中 GATA3 的内在表达对于其在炎症部位的积累能力以及在各种极化或炎症环境中维持高 Foxp3 表达水平是必需的。此外，我们的数据表明，GATA3 限制 Treg 向效应 T 细胞表型的极化，并在炎症组织中获得效应细胞因子。总的来说，我们的工作揭示了 GATA3 在 T 细胞中的复杂作用的一个新方面，并强调了其在控制炎症过程中 Treg 生理学方面的基本作用。
