Promiscuous Foxp3-cre activity reveals a differential requirement for CD28 in Foxp3⁺ and Foxp3⁻ T cells.
Promiscuous Foxp3-cre activity reveals a differential requirement for CD28 in Foxp3⁺ and Foxp3⁻ T cells.
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DOI：
10.1038/icb.2014.108
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发表时间：
2015-04
影响因子：
4
通讯作者：
Schlenner, Susan M.
中科院分区：
文献类型：
--
作者：
Franckaert, Dean;Dooley, James;Roos, Evelyne;Floess, Stefan;Huehn, Jochen;Luche, Herve;Fehling, Hans Joerg;Liston, Adrian;Linterman, Michelle A.;Schlenner, Susan M.
CD 28的共刺激信号对于胸腺调节性T细胞（Treg）的发育至关重要。为了确定胸腺选择后CD 28与外周Treg的功能相关性，我们将广泛使用的叉头盒蛋白3（Foxp 3）-CreYFP小鼠与携带条件性Cd 28等位基因的小鼠杂交。Treg特异性CD 28缺陷引起严重的自身免疫综合征，这是由于CD 28缺陷型Treg在竞争适应性和增殖方面的强烈劣势。相比之下，Treg存活和谱系完整性不受缺乏CD 28的影响。该数据表明，即使在初始诱导要求之后，Treg也比常规T细胞维持更高的对CD 28信号传导的依赖性以实现稳态。此外，我们发现Foxp 3-CreYFP等位基因是一种低型，Foxp 3蛋白水平降低。此外，我们在这里报告的随机活动的Foxp 3-CreYFP等位基因在非甲状腺肿，足以重组一些条件等位基因（包括Cd 28），但不是其他（包括R26-RFP）。当分析条件突变的Treg时，应考虑Foxp 3-CreYFP等位基因的这种亚型和“泄漏”表达。
Costimulatory signals by CD28 are critical for thymic regulatory T-cell (Treg) development. To determine the functional relevance of CD28 for peripheral Treg post thymic selection, we crossed the widely used Forkhead box protein 3 (Foxp3)-CreYFP mice to mice bearing a conditional Cd28 allele. Treg-specific CD28 deficiency provoked a severe autoimmune syndrome as a result of a strong disadvantage in competitive fitness and proliferation of CD28-deficient Tregs. By contrast, Treg survival and lineage integrity were not affected by the lack of CD28. This data demonstrate that, even after the initial induction requirement, Treg maintain a higher dependency on CD28 signalling than conventional T cells for homeostasis. In addition, we found the Foxp3-CreYFP allele to be a hypomorph, with reduced Foxp3 protein levels. Furthermore, we report here the stochastic activity of the Foxp3-CreYFP allele in non-Tregs, sufficient to recombine some conditional alleles (including Cd28) but not others (including R26-RFP). This hypomorphism and ‘leaky' expression of the Foxp3-CreYFP allele should be considered when analysing the conditionally mutated Treg.
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影响因子：
64.8
作者：
Wan, Yisong Y.;Flavell, Richard A.
通讯作者：
Flavell, Richard A.
影响因子：
15.9
作者：
Zhang, Ruan;Huynh, Alexandria;Turka, Laurence A.
通讯作者：
Turka, Laurence A.
影响因子：
7.7
作者：
Linterman MA;Denton AE;Divekar DP;Zvetkova I;Kane L;Ferreira C;Veldhoen M;Clare S;Dougan G;Espéli M;Smith KG
通讯作者：
Smith KG
影响因子：
5.3
作者：
JUNE, CH;LEDBETTER, JA;THOMPSON, CB
通讯作者：
THOMPSON, CB
影响因子：
4.4
作者：
Tang, QZ;Henriksen, KJ;Bluestone, JA
通讯作者：
Bluestone, JA