Helios is associated with CD4 T cells differentiating to T helper 2 and follicular helper T cells in vivo independently of Foxp3 expression.
Helios is associated with CD4 T cells differentiating to T helper 2 and follicular helper T cells in vivo independently of Foxp3 expression.
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DOI：
10.1371/journal.pone.0020731
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Mohr E
中科院分区：
文献类型：
--
作者：
Serre K;Bénézech C;Desanti G;Bobat S;Toellner KM;Bird R;Chan S;Kastner P;Cunningham AF;Maclennan IC;Mohr E
尽管体外IL-4指导CD 4 T细胞产生辅助性T细胞2（Th 2）细胞因子，但这些细胞因子可以在缺乏IL-4信号传导的情况下在体内诱导。因此，不同于体外Th 2诱导途径的机制有助于体内Th 2分化。体内IL-4非依赖性Th 2分化的途径尚未被表征。Helios（ikzf 2）是Ikaros转录调节因子家族的成员，在胸腺细胞和一些抗原成熟T细胞以及调节性T细胞中表达。已经提出Helios是胸腺衍生的调节性T细胞的特异性标志物。在这里，我们表明，小鼠卵清蛋白特异性CD 4（OTII）细胞响应明矾沉淀卵清蛋白（alumOVA）上调Th 2功能-加塔-3和IL-4 -以及Helios mRNA和蛋白质。Helios在这种反应中也在滤泡辅助T（TFh）细胞中上调。相比之下，OTII细胞对Th 1抗原-表达活的减毒卵清蛋白的沙门氏菌-的应答上调Th 1特征- T-bet和IFN-γ，但不上调Helios。此外，体外诱导产生Th 2细胞因子的CD 4 T细胞不表达Helios。Helios mRNA和蛋白诱导的动力学反映了加塔-3的动力学。alumOVA诱导IL-4、IL-13和CXCR 5需要NF-κB1，这也是Helios上调所需的。重要的是，Helios在Th 2和TFh细胞中被诱导，而Foxp 3没有平行上调。这些研究结果表明，在响应明矾蛋白疫苗的Th 2和TFh的发展中，Helios发挥了关键作用。我们使用Helios缺陷型OTII细胞测试了这种可能性，发现这种缺陷对响应alumOVA的Th 2和TFh分化没有明显影响。Helios在Th 2和TFh对明矾蛋白疫苗的体内应答期间在CD 4 T细胞中选择性上调，但这种上调的功能意义仍不确定。
Although in vitro IL-4 directs CD4 T cells to produce T helper 2 (Th2)-cytokines, these cytokines can be induced in vivo in the absence of IL-4-signalling. Thus, mechanism(s), different from the in vitro pathway for Th2-induction, contribute to in vivo Th2-differentiation. The pathway for in vivo IL-4-independent Th2-differentiation has yet to be characterized. Helios (ikzf2), a member of the Ikaros transcription regulator family, is expressed in thymocytes and some antigen-matured T cells as well as in regulatory T cells. It has been proposed that Helios is a specific marker for thymus-derived regulatory T cells. Here, we show that mouse ovalbumin-specific CD4 (OTII) cells responding to alum-precipitated ovalbumin (alumOVA) upregulate Th2 features - GATA-3 and IL-4 - as well as Helios mRNA and protein. Helios is also upregulated in follicular helper T (TFh) cells in this response. By contrast, OTII cells responding to the Th1 antigen - live attenuated ovalbumin-expressing Salmonella - upregulate Th1 features - T-bet and IFN-γ - but not Helios. In addition, CD4 T cells induced to produce Th2 cytokines in vitro do not express Helios. The kinetics of Helios mRNA and protein induction mirrors that of GATA-3. The induction of IL-4, IL-13 and CXCR5 by alumOVA requires NF-κB1 and this is also needed for Helios upregulation. Importantly, Helios is induced in Th2 and TFh cells without parallel upregulation of Foxp3. These findings suggested a key role for Helios in Th2 and TFh development in response to alum-protein vaccines. We tested this possibility using Helios-deficient OTII cells and found this deficiency had no discernable impact on Th2 and TFh differentiation in response to alumOVA. Helios is selectively upregulated in CD4 T cells during Th2 and TFh responses to alum-protein vaccines in vivo, but the functional significance of this upregulation remains uncertain.
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影响因子：
32.4
作者：
Hill, Jonathan A.;Feuerer, Markus;Benoist, Christophe
通讯作者：
Benoist, Christophe
影响因子：
4.4
作者：
Cunningham, AF;Fallon, PG;Toellner, KM
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影响因子：
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作者：
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30.8
作者：
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Stefansson, Kari
影响因子：
3.6
作者：
Getnet D;Grosso JF;Goldberg MV;Harris TJ;Yen HR;Bruno TC;Durham NM;Hipkiss EL;Pyle KJ;Wada S;Pan F;Pardoll DM;Drake CG
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Drake CG