The Temporal and Spatial Dynamics of Foxp3+Treg Cell-Mediated Suppression during Contact Hypersensitivity Responses in a Murine Model
The Temporal and Spatial Dynamics of Foxp3+Treg Cell-Mediated Suppression during Contact Hypersensitivity Responses in a Murine Model
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DOI：
10.1038/jid.2012.212
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发表时间：
2012-12-01
影响因子：
6.5
通讯作者：
Fyhrquist, Nanna
中科院分区：
文献类型：
--
作者：
Lehtimaki, Sari;Savinko, Terhi;Fyhrquist, Nanna
调节性T(Treg)细胞抑制接触性超敏反应(CHS)，但其作用的动力学、模式和部位尚不清楚。我们研究了调节性T细胞(DEREG)条件Foxp3基因敲除小鼠在CHS反应中的叉头盒P3+(Foxp3+)Treg细胞，其中Foxp3+细胞可以被白喉毒素瞬时删除。用恶唑酮致敏和激发小鼠，Foxp3+细胞在致敏或激发过程中均被耗尽。致敏前Treg细胞耗尽导致CHS反应显著加重和延长。相反，在激发过程中消耗Treg细胞对24小时反应没有影响，但反应显著延长。在野生型小鼠中，CHS反应的逐渐缓解伴随着类似的Foxp3+Treg细胞相对于T效应细胞在皮肤中的逐渐积累。这一效应在Treg细胞耗尽的小鼠中并不明显，这表明皮肤是Treg细胞在分解阶段活动的重要部位。综上所述，我们的结果表明，内源性Foxp3+Treg细胞的功能在敏化和溶解阶段是重要的，但它们在激发前的耗尽并不影响激发后最初24小时的CHS反应。《皮肤病研究杂志》(2012年)1322744-2751；doi：10.1038/jid.2012.212；2012年6月28日在线发布
Regulatory T (Treg) cells suppress contact hypersensitivity (CHS) responses, but the dynamics, mode, and site of their action is not well characterized. We studied forkhead box P3+ (Foxp3+) Treg cells during the CHS response in conditional Foxp3 knockout depletion of regulatory T cell (DEREG) mice, where Foxp3+ cells can be transiently deleted by diphtheria toxin. The mice were sensitized and challenged with oxazolone, and Foxp3+ cells were depleted either during sensitization or elicitation. Treg cell depletion before sensitization led to significantly exacerbated and prolonged CHS responses. In contrast, depleting Treg cells during elicitation had no effect on the 24-hour response, but the response was significantly prolonged. In wild-type mice, the gradual resolution of the CHS response was accompanied by a similarly gradual accumulation of Foxp3+ Treg cells relative to T effector cells in the skin. This effect was not as marked in the Treg cell-depleted mice, suggesting that the skin is an important site of Treg cell activities during the resolution phase. Together, our results show that endogenous Foxp3+ Treg cell function is important during the sensitization and resolution phases, but their depletion just before elicitation does not have an effect on the CHS response during the first 24 hours after elicitation. Journal of Investigative Dermatology (2012) 132, 2744-2751; doi:10.1038/jid.2012.212; published online 28 June 2012