Diversification and senescence of Foxp3+ regulatory T cells during experimental autoimmune encephalomyelitis.
Diversification and senescence of Foxp3+ regulatory T cells during experimental autoimmune encephalomyelitis.
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DOI：
10.1002/eji.201242881
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发表时间：
2013-05
影响因子：
5.4
通讯作者：
Geiger, Terrence L.
中科院分区：
文献类型：
--
作者：
Tauro, Sharyn;Phuong Nguyen;Li, Bofeng;Geiger, Terrence L.
Foxp 3+调节性T细胞（Treg）在自身免疫期间应答的命运尚未明确。我们观察到实验性自身免疫性脑脊髓炎（EAE）中KLRG 1 + CNS浸润性Treg显著升高，并评估了其起源和性质。与KLRG 1 −细胞相比，KLRG 1 + Treg细胞的活化标志物表达、Foxp 3和CD 25水平增加，细胞周期更快。KLRG 1 − Treg转化为KLRG 1+细胞，这在自身免疫性炎症的背景下增加。转化是单向的; KLRG 1 + Treg没有恢复到KLRG 1 −状态。KLRG 1+而不是KLRG 1 − Treg存活较差，表明终末分化。这与BCL 2减少和分离细胞的凋亡增加有关。KLRG 1在培养物中的iTreg上没有上调，但在转移和EAE诱导后或在EAE期间自发形成的iTreg上上调。与KLRG 1 − Treg相比，KLRG 1 + Treg产生更多的IL 10，并改变了效应细胞因子的产生。尽管存在差异，但KLRG 1+和KLRG 1 − Treg在抑制EAE方面表现出相似的效力。KLRG 1+和KLRG 1 −群体在表型上是异质的，活化标志物表达的程度和模式取决于细胞位置和炎症。我们的研究结果支持EAE期间Treg的广泛多样化，并将KLRG 1与自身免疫期间Treg功能改变和衰老联系起来。
The fate of Foxp3+ regulatory T cells (Treg) responding during autoimmunity is not well defined. We observed a marked elevation in KLRG1+ CNS-infiltrating Treg in experimental autoimmune encephalomyelitis (EAE), and assessed their origin and properties. KLRG1+ Treg showed increased activation marker expression, Foxp3 and CD25 levels, and more rapid cell cycling than KLRG1− cells. KLRG1− Treg converted into KLRG1+ cells and this was increased in the context of autoimmune inflammation. Conversion was unidirectional; KLRG1+ Treg did not revert to a KLRG1− state. KLRG1+ but not KLRG1− Treg survived poorly, indicative of terminal differentiation. This was associated with diminished BCL2 and increased apoptosis of isolated cells. KLRG1 was not upregulated on iTreg in culture, but was after transfer and EAE induction or on iTreg developing spontaneously during EAE. KLRG1+ Treg produced more IL10 and had altered effector cytokine production compared with KLRG1− Treg. Despite their differences, KLRG1+ and KLRG1− Treg proved similarly potent in suppressing EAE. KLRG1+ and KLRG1− populations were phenotypically heterogeneous, with the extent and pattern of activation marker expression dependent both on cellular location and inflammation. Our results support an extensive diversification of Treg during EAE, and associate KLRG1 with altered Treg function and senescence during autoimmunity.
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影响因子：
32.4
作者：
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