Differential Roles of IL-2 Signaling in Developing versus Mature Tregs.
Differential Roles of IL-2 Signaling in Developing versus Mature Tregs.
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DOI：
10.1016/j.celrep.2018.10.002
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发表时间：
2018-10-30
期刊：
影响因子：
8.8
通讯作者：
Turka LA
中科院分区：
文献类型：
--
作者：
Fan MY;Low JS;Tanimine N;Finn KK;Priyadharshini B;Germana SK;Kaech SM;Turka LA
尽管Foxp3+调节性T细胞(Tregs)的发育需要白介素2(IL-2)，但在成熟Tregs中是否需要持续的IL-2信号来维持谱系稳定、存活和抑制功能尚不清楚。在我们培育的小鼠中，IL-2受体的主要配体结合亚单位CD25可以在胸腺发育后从树突状细胞中诱导删除。与Treg发育相比，我们发现IL-2对于维持成熟Treg的谱系稳定是必不可少的。尽管长期的Treg存活需要持续的IL-2信号，但在使用IL-7的体内，CD25缺失的Treg可能会持续数周。我们还观察到CD25缺失后糖酵解代谢和抑制功能的缺陷。因此，与发育中IL-2的主要作用是启动Foxp3表达的Treg不同，成熟Treg需要持续的IL-2信号来维持生存和抑制功能，而不是维持谱系稳定。白介素2(IL-2)对调节性T细胞(Treg)的发育非常重要，被认为是Treg存活和谱系稳定所必需的。在这里，Fan等人。表明IL-2实际上对体内Treg血统的维持是必不可少的，而Treg在使用IL-7的体内可能会持续更长的时间。
Although Foxp3+ regulatory T cells (Tregs) require interleukin-2 (IL-2) for their development, it has been unclear whether continuing IL-2 signals are needed to maintain lineage stability, survival, and suppressor function in mature Tregs. We generated mice in which CD25, the main ligand-binding subunit of the IL-2 receptor, can be inducibly deleted from Tregs after thymic development. In contrast to Treg development, we find that IL-2 is dispensable for maintaining lineage stability in mature Tregs. Although continuous IL-2 signaling is needed for long-term Treg survival, CD25-deleted Tregs may persist for several weeks in vivo using IL-7. We also observe defects in glycolytic metabolism and suppressor function following CD25 deletion. Thus, unlike developing Tregs in which the primary role of IL-2 is to initiate Foxp3 expression, mature Tregs require continuous IL-2 signaling to maintain survival and suppressor function, but not to maintain lineage stability. Interleukin-2 (IL-2) is important for regulatory T cell (Treg) development and is believed to be necessary for Treg survival and lineage stability. Here, Fan et al. show that IL-2 is in fact dispensable for Treg lineage maintenance in vivo and that Tregs may persist for an extended time in vivo using IL-7.
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影响因子：
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DOI：
10.1073/pnas.0601335103
发表时间：
2006-04-11
影响因子：
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作者：
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通讯作者：
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影响因子：
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