Interleukin-12 converts Foxp3+ regulatory T cells to interferon-γ-producing Foxp3+ T cells that inhibit colitis.
Interleukin-12 converts Foxp3+ regulatory T cells to interferon-γ-producing Foxp3+ T cells that inhibit colitis.
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DOI：
10.1053/j.gastro.2011.03.009
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发表时间：
2011-06
期刊：
影响因子：
29.4
通讯作者：
Cong Y
中科院分区：
文献类型：
--
作者：
Feng T;Cao AT;Weaver CT;Elson CO;Cong Y
调节性T（Treg）细胞是可塑性的，但它们转化为Foxp 3+干扰素（IFN）-γ+ T细胞的体内机制以及这些转化的细胞是否保留抑制结肠炎的能力尚不清楚。Foxp 3 + Treg细胞通过培养来自Foxp 3GFP CBir 1 T细胞受体（TCR）转基因（CBir 1-Tg）小鼠的幼稚CD 4 + T细胞与转化生长因子（TGF）-β产生，所述小鼠对CBir 1鞭毛蛋白（一种免疫显性微生物群抗原）具有特异性。通过荧光激活细胞分选分离Foxp 3GFP + CBir 1-Tg Treg细胞，并转移到TCRβxδ−/−小鼠中。通过将幼稚CBir 1-Tg CD 4 + T细胞转移到免疫缺陷小鼠中来诱导结肠炎。微生物群抗原特异性Foxp 3 + Treg细胞在肠中转化为IFN-γ+辅助性T（Th）1细胞、白介素（IL）-17+ Th 17细胞和共表达IFN-γ和/或IL-17的Foxp 3 + T细胞。Treg细胞转化为产生IFN-γ的Th 1细胞和Foxp 3 +IFN-γ+ T细胞需要肠道中的先天性细胞产生IL-12;用抗体阻断IL-12可抑制Treg细胞受体小鼠肠道中的Th 1和Foxp 3 +IFN-γ+ T细胞转化。在体外，IL-12而非IL-23的添加促进Treg细胞转化为Th 1和Foxp 3 +IFN-γ+ T细胞。Foxp 3 +IFN-γ+ T细胞具有调节活性，因为它们在体外抑制幼稚T细胞的增殖，并抑制微生物群抗原特异性T细胞诱导结肠炎。IFN-γ+ Th 1细胞不转化为Treg细胞; Foxp 3 +IFN-γ+ T细胞分化为IFN-γ+ T细胞，但不分化为Foxp 3 + T细胞。IL-12促进Treg细胞转化为IFN-γ表达细胞; Foxp 3 +IFN-γ+ T细胞保留其调节功能，并在Foxp 3 + Treg细胞转化为IFN-γ+ Th 1细胞期间发育。
Regulatory T (Treg) cells are plastic, but the in vivo mechanisms by which they are converted into Foxp3+interferon (IFN)-γ+ T cells, and whether these converted cells retain the ability to inhibit colitis, are not clear. Foxp3+ Treg cells were generated by culture of naïve CD4+ T cells from Foxp3GFP CBir1 T-cell receptor (TCR) transgenic (CBir1-Tg) mice, which are specific for CBir1 flagellin (an immunodominant microbiota antigen), with transforming growth factor (TGF)-β. Foxp3GFP+ CBir1-Tg Treg cells were isolated by fluorescence-activated cell sorting and transferred into TCRβxδ−/− mice. Colitis was induced by transfer of naïve CBir1-Tg CD4+ T cells into immunodeficient mice. Microbiota antigen-specific Foxp3+ Treg cells were converted, in the intestine, to IFN-γ+ T-helper (Th)1 cells, interleukin (IL)-17+ Th17 cells, and Foxp3+ T cells that coexpress IFN-γ and/or IL-17. Conversion of Treg cells into IFN-γ-producing Th1 cells and Foxp3+IFN-γ+ T cells required innate cell production of IL-12 in the intestine; blocking IL-12 with an antibody inhibited their conversion to Th1 and Foxp3+IFN-γ+ T cells in the intestines of mice that were recipients of Treg cells. Addition of IL-12, but not IL-23, promoted conversion of Treg cells into Th1 and Foxp3+IFN-γ+ T cells, in vitro. Foxp3+IFN-γ+ T cells had regulatory activity, because they suppressed proliferation of naïve T cells, in vitro, and inhibited induction of colitis by microbiota antigen-specific T cells. IFN-γ+ Th1 cells were not converted into Treg cells; Foxp3+IFN-γ+ T cells differentiated into IFN-γ+ but not Foxp3+ T cells. IL-12 promotes conversion of Treg cells into IFN-γ-expressing cells; Foxp3+IFN-γ+ T cells retain their regulatory functions and develop during the transition of Foxp3+ Treg cells into IFN-γ+ Th1 cells.
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DOI：
10.1084/jem.20092253
发表时间：
2010-06-07
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Feng T;Wang L;Schoeb TR;Elson CO;Cong Y
通讯作者：
Cong Y
影响因子：
5.4
作者：
Osorio, Fabiola;LeibundGut-Landmann, Salome;Lochner, Matthias;Lahl, Katharina;Sparwasser, Tim;Eberl, Gerard;Reis e Sousa, Caetano
通讯作者：
Reis e Sousa, Caetano
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：
Xu, LiLi;Kitani, Atsushi;Strober, Warren
通讯作者：
Strober, Warren
影响因子：
64.8
作者：
Gavin, Marc A.;Rasmussen, Jeffrey P.;Rudensky, Alexander Y.
通讯作者：
Rudensky, Alexander Y.