Plasticity of Foxp3+ T Cells Reflects Promiscuous Foxp3 Expression in Conventional T Cells but Not Reprogramming of Regulatory T Cells
Plasticity of Foxp3+ T Cells Reflects Promiscuous Foxp3 Expression in Conventional T Cells but Not Reprogramming of Regulatory T Cells
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DOI：
10.1016/j.immuni.2011.12.012
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发表时间：
2012-02-24
期刊：
影响因子：
32.4
通讯作者：
Hori, Shohei
中科院分区：
文献类型：
--
作者：
Miyao, Takahisa;Floess, Stefan;Hori, Shohei
环境诱导的Foxp3(+)调节性T(Treg)细胞重新编程为辅助性T(Th)细胞的新兴概念仍然存在争议。通过遗传命运图谱或过继转移，我们发现了一小部分非调节性Foxp3(+)T细胞，表现出混乱和瞬时的Foxp3表达，这些细胞产生Foxp3(-)(“exFoxp3”)Th细胞，并选择性地聚集在炎性细胞因子环境或淋巴细胞减少的环境中，包括处于个体发育早期的细胞。相比之下，Treg细胞在这些条件下没有经历重新编程，无论它们来自胸腺或外周。此外，尽管少数Treg细胞暂时失去了Foxp3的表达，但这种“潜伏的”Treg细胞保留了他们的记忆，并在激活后强劲地重新表达Foxp3和抑制功能。本研究证实了Treg细胞构成了一个稳定的细胞谱系，其在不断变化的环境中的承诺状态是由Foxp3基因座的DNA去甲基化保证的，与正在进行的Foxp3表达无关。
The emerging notion of environment-induced reprogramming of Foxp3(+) regulatory T (Treg) cells into helper T (Th) cells remains controversial. By genetic fate mapping or adoptive transfers, we have identified a minor population of nonregulatory Foxp3(+) T cells exhibiting promiscuous and transient Foxp3 expression, which gave rise to Foxp3(-) ("exFoxp3") Th cells and selectively accumulated in inflammatory cytokine milieus or in lymphopenic environments including those in early ontogeny. In contrast, Treg cells did not undergo reprogramming under those conditions irrespective of their thymic or peripheral origins. Moreover, although a few Treg cells transiently lose Foxp3 expression, such "latent" Treg cells retained their memory and robustly reexpressed Foxp3 and suppressive function upon activation. This study establishes that Treg cells constitute a stable cell lineage, whose committed state in a changing environment is ensured by DNA demethylation of the Foxp3 locus irrespectively of ongoing Foxp3 expression.