STAT5 is a potent negative regulator of TFH cell differentiation.
STAT5 is a potent negative regulator of TFH cell differentiation.
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DOI：
10.1084/jem.20111174
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发表时间：
2012-02-13
期刊：
影响因子：
--
通讯作者：
Crotty S
中科院分区：
文献类型：
--
作者：
Johnston RJ;Choi YS;Diamond JA;Yang JA;Crotty S
白细胞介素2、信号转导及转录激活因子5（STAT5）和Blimp - 1共同作用抑制小鼠滤泡辅助性T细胞的分化。
滤泡辅助性T细胞（TFH细胞）是一种CD4 + T细胞亚群，专门为生发中心（GC）B细胞提供辅助，从而介导长效体液免疫的发展。TFH细胞分化由转录因子Bcl6驱动，近期研究已确定了驱动Bcl6表达的细胞因子和细胞间信号。然而，尽管TFH细胞失调与几种主要的自身免疫性疾病有关，但TFH细胞分化的负调控机制却鲜为人知。在本研究中，我们发现STAT5抑制TFH细胞的分化和功能。活化的CD4 + T细胞中的持续性STAT5信号传导选择性地阻断了TFH细胞分化和生发中心的形成，并且白细胞介素 - 2信号传导是该途径的主要诱导因素。相反，STAT5缺陷型CD4 + T细胞（用表达Cre的载体转导的成熟STAT5fl/fl CD4 + T细胞）在体内T细胞启动过程中迅速上调Bcl6表达，并优先分化为TFH细胞。在缺乏转录因子Blimp - 1（Bcl6表达和TFH细胞分化的直接抑制因子）的情况下，STAT5信号传导无法抑制TFH细胞分化。这些结果表明，白细胞介素2、STAT5和Blimp - 1协同负调控TFH细胞分化。
Interleukin 2, STAT5, and Blimp-1 work together to suppress differentiation of follicular helper T cells in mice. Follicular helper T cells (TFH cells) constitute the CD4+ T cell subset that is specialized to provide help to germinal center (GC) B cells and, consequently, mediate the development of long-lived humoral immunity. TFH cell differentiation is driven by the transcription factor Bcl6, and recent studies have identified cytokine and cell–cell signals that drive Bcl6 expression. However, although TFH dysregulation is associated with several major autoimmune diseases, the mechanisms underlying the negative regulation of TFH cell differentiation are poorly understood. In this study, we show that STAT5 inhibits TFH cell differentiation and function. Constitutive STAT5 signaling in activated CD4+ T cells selectively blocked TFH cell differentiation and GCs, and IL-2 signaling was a primary inducer of this pathway. Conversely, STAT5-deficient CD4+ T cells (mature STAT5fl/fl CD4+ T cells transduced with a Cre-expressing vector) rapidly up-regulated Bcl6 expression and preferentially differentiated into TFH cells during T cell priming in vivo. STAT5 signaling failed to inhibit TFH cell differentiation in the absence of the transcription factor Blimp-1, a direct repressor of Bcl6 expression and TFH cell differentiation. These results demonstrate that IL-2, STAT5, and Blimp-1 collaborate to negatively regulate TFH cell differentiation.
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影响因子：
4.4
作者：
Burchill, Matthew A.;Yang, Jianying;Farrar, Michael A.
通讯作者：
Farrar, Michael A.
影响因子：
32.4
作者：
Choi YS;Kageyama R;Eto D;Escobar TC;Johnston RJ;Monticelli L;Lao C;Crotty S
通讯作者：
Crotty S
影响因子：
30.5
作者：
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--
DOI：
10.1073/pnas.0911573106
发表时间：
2009-12-01
影响因子：
11.1
作者：
Gigoux, Mathieu;Shang, Jijun;Suh, Woong-Kyung
通讯作者：
Suh, Woong-Kyung
影响因子：
48
作者：
Ai, Hui-wang;Hazelwood, Kristin L.;Campbell, Robert E.
通讯作者：
Campbell, Robert E.