T-bet(+) Treg cells undergo abortive Th1 cell differentiation due to impaired expression of IL-12 receptor β2.
T-bet(+) Treg cells undergo abortive Th1 cell differentiation due to impaired expression of IL-12 receptor β2.
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DOI：
10.1016/j.immuni.2012.05.031
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发表时间：
2012-09-21
期刊：
影响因子：
32.4
通讯作者：
Campbell DJ
中科院分区：
文献类型：
--
作者：
Koch MA;Thomas KR;Perdue NR;Smigiel KS;Srivastava S;Campbell DJ
Foxp 3+调节性T（Treg）细胞限制炎症反应并维持免疫稳态。虽然由几个表型和功能不同的亚群组成，但外周内特化Treg细胞群的分化特征很差。我们证明，T-bet+ Treg细胞的发展，有效地抑制辅助性T细胞1（Th 1）的细胞反应是依赖于转录因子STAT 1，并直接发生在响应干扰素-γ产生的效应T细胞。此外，STAT 1激活后IL-12 R β2受体组分的延迟诱导有助于确保Treg细胞不容易完成STAT 4依赖性Th 1细胞发育，并失去其抑制效应T细胞增殖的能力。因此，我们定义了一个流产的Th 1细胞发育的途径，导致外周Treg细胞的专业化，并证明了一个单一的细胞因子受体的表达受损，有助于维持Treg细胞抑制功能的炎症性Th 1细胞反应的背景下。Treg细胞对T细胞衍生的IFN-γ进行功能特化Treg细胞对IL-12无体外应答Treg细胞中IL-12 rb 2的表达延迟降低的IL-12应答性阻止Treg细胞完成Th 1细胞发育
Foxp3+ regulatory T (Treg) cells limit inflammatory responses and maintain immune homeostasis. Although comprised of several phenotypically and functionally distinct subsets, the differentiation of specialized Treg cell populations within the periphery is poorly characterized. We demonstrate that the development of T-bet+ Treg cells that potently inhibit T helper 1 (Th1) cell responses was dependent on the transcription factor STAT1 and occurred directly in response to interferon-γ produced by effector T cells. Additionally, delayed induction of the IL-12Rβ2 receptor component after STAT1 activation helped ensure that Treg cells do not readily complete STAT4-dependent Th1 cell development and lose their ability to suppress effector T cell proliferation. Thus, we define a pathway of abortive Th1 cell development that results in the specialization of peripheral Treg cells and demonstrate that impaired expression of a single cytokine receptor helps maintain Treg cell-suppressive function in the context of inflammatory Th1 cell responses. ► Treg cells undergo functional specialization in response to T cell-derived IFN-γ ► Treg cells are not responsive to IL-12 ex vivo ► Expression of Il12rb2 is delayed in Treg cells ► Reduced IL-12 responsiveness prevents Treg cells from completing Th1 cell development
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影响因子：
64.8
作者：
Marson, Alexander;Kretschmer, Karsten;Young, Richard A.
通讯作者：
Young, Richard A.
DOI：
10.1084/jem.177.4.1199
发表时间：
1993-04-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Manetti R;Parronchi P;Giudizi MG;Piccinni MP;Maggi E;Trinchieri G;Romagnani S
通讯作者：
Romagnani S
影响因子：
82.9
作者：
Korn, Thomas;Reddy, Jayagopala;Kuchroo, Vijay K.
通讯作者：
Kuchroo, Vijay K.
影响因子：
4.4
作者：
McGeachy, MJ;Stephens, LA;Anderton, SM
通讯作者：
Anderton, SM
影响因子：
15.3
作者：
Szabo, SJ;Dighe, AS;Gubler, U;Murphy, KM
通讯作者：
Murphy, KM