激动剂驱动的CD4+CD25+Foxp3+调节性T细胞的发育需要由Stat6介导的第二信号。
Agonist-driven development of CD4+CD25+Foxp3+ regulatory T cells requires a second signal mediated by Stat6.
作者信息
Sanchez-Guajardo Vanesa, Tanchot Corinne, O'Malley John T, Kaplan Mark H, Garcia Sylvie, Freitas Antonio A
机构信息
Unité de Biologie des Populations Lymphocytaires, Centre National de la Recherche Scientifique, Institut Pasteur, 25 rue du Dr. Roux, 75015 Paris, France.
出版信息
J Immunol. 2007 Jun 15;178(12):7550-6. doi: 10.4049/jimmunol.178.12.7550.
The factors that induce Foxp3 expression and regulatory T (Treg) cell development remain unknown. In this study, we investigated the role of STAT4 and STAT6 in agonist-driven generation of Ag-specific Foxp3-expressing Treg cells. Our findings indicate that fully efficient induction of Foxp3 expression and development of Ag-specific Treg cells requires the synergistic action of two signals: a TCR-mediated signal and a second signal mediated by STAT6. Indeed, by comparing the development of wild-type and STAT4- and STAT6-deficient hemagglutinin-specific T cells in the presence of hemagglutinin Ag, we found that the absence of STAT6 impaired the generation of Ag-specific CD4+CD25+Foxp3+ cells. Moreover, in transgenic mice expressing a constitutively active form of STAT6, we found that the fraction of CD4+Foxp3+ cells exceeds that of control wild-type littermates. Overall these findings support a role for the STAT6 pathway in Treg cell development and maintenance.
诱导Foxp3表达和调节性T（Treg）细胞发育的因素尚不清楚。在本研究中，我们调查了信号转导和转录激活因子4（STAT4）及信号转导和转录激活因子6（STAT6）在激动剂驱动的抗原特异性表达Foxp3的Treg细胞生成中的作用。我们的研究结果表明，Foxp3表达的完全有效诱导及抗原特异性Treg细胞的发育需要两种信号的协同作用：一种是T细胞受体（TCR）介导的信号，另一种是由STAT6介导的第二信号。事实上，通过比较在存在血凝素抗原的情况下野生型、STAT4缺陷型和STAT6缺陷型血凝素特异性T细胞的发育情况，我们发现STAT6的缺失会损害抗原特异性CD4⁺CD25⁺Foxp3⁺细胞的生成。此外，在表达组成型活性形式STAT6的转基因小鼠中，我们发现CD4⁺Foxp3⁺细胞的比例超过了对照野生型同窝小鼠。总体而言，这些发现支持STAT6信号通路在Treg细胞发育和维持中的作用。
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