TGF-β converts Th1 cells into Th17 cells through stimulation of Runx1 expression.
TGF-β converts Th1 cells into Th17 cells through stimulation of Runx1 expression.
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DOI：
10.1002/eji.201444726
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发表时间：
2015-04
影响因子：
5.4
通讯作者：
Cong, Yingzi
中科院分区：
文献类型：
--
作者：
Liu, Hou-Pu;Cao, Anthony T.;Feng, Ting;Li, Qingjie;Zhang, Wenbo;Yao, Suxia;Dann, Sara M.;Elson, Charles O.;Cong, Yingzi
分化的CD 4 + T细胞在各种条件下保持可塑性。然而，Th 1细胞的稳定性尚不清楚，也不清楚Th 1细胞是否可以转化为Th 17细胞，从而促进IFN-γ+IL-17+ CD 4 + T细胞的产生，其数量与结肠炎的严重程度相关。我们研究了IFN-γ+ Th 1细胞在肠道炎症状态下能否转化为Th 17细胞及其机制。IFN-γThy1.1+ Th 1细胞通过在Th 1极化条件下培养来自IFN-γThy1.1 CBir 1 TCR-Tg报告小鼠的幼稚CD 4 + T细胞产生，所述报告小鼠的TCR对免疫显性微生物群抗原CBir 1鞭毛蛋白具有特异性。在过继转移后，IFN-γThy1.1+ Th 1细胞在Rag−/−小鼠中诱导结肠炎，并在发炎的肠道中转化为IL-17+ Th 17，但不转化为Foxp 3 +Treg细胞。TGF-β和IL-6，而不是IL-1β和IL-23，调节Th 1转化为Th 17细胞。TGF-β对转录因子Runx 1的诱导对于转化至关重要，因为通过siRNA沉默Runx 1抑制了Th 1转化为Th 17细胞。此外，TGF-β增强组蛋白H3 K9乙酰化，但抑制Th 1细胞中il-17或rorc基因上Runx 1和RORγ t结合位点的H3 K9三甲基化。我们的结论是，在肠道炎症条件下，Th 1细胞转化为Th 17细胞，这可能是由TGF-β诱导Runx 1介导的。
Differentiated CD4+ T cells preserve plasticity under various conditions. However, the stability of Th1 cells is unclear, as is whether Th1 cells can convert into Th17 cells and thereby contribute to the generation of IFN-γ+IL-17+CD4+ T cells, the number of which correlates with severity of colitis. We investigated whether IFN-γ+Th1 cells can convert into Th17 cells under intestinal inflammation and the mechanisms involved. IFN-γThy1.1+ Th1 cells were generated by culturing naïve CD4+ T cells from IFN-γThy1.1 CBir1 TCR-Tg reporter mice, whose TCR is specific for an immunodominant microbiota antigen, CBir1 flagellin, under Th1 polarizing conditions. IFN-γThy1.1+ Th1 cells induced colitis in Rag−/− mice after adoptive transfer and converted into IL-17+Th17, but not Foxp3+Treg cells in the inflamed intestines. TGF-β and IL-6, but not IL-1β and IL-23, regulated Th1 conversion into Th17 cells. TGF-β induction of transcriptional factor Runx1 is crucial for the conversion, since silencing Runx1 by siRNA inhibited Th1 conversion into Th17 cells. Furthermore, TGF-β enhanced histone H3K9 acetylation but inhibited H3K9 trimethylation of Runx1- and RORγt-binding sites on il-17 or rorc genes in Th1 cells. We conclude that Th1 cells convert into Th17 cells under inflammatory conditions in intestines, which is possibly mediated by TGF-β induction of Runx1.
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影响因子：
4.4
作者：
Panzer, Marc;Sitte, Selina;Voehringer, David
通讯作者：
Voehringer, David
DOI：
10.1084/jem.20070663
发表时间：
2007-08-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Annunziato F;Cosmi L;Santarlasci V;Maggi L;Liotta F;Mazzinghi B;Parente E;Filì L;Ferri S;Frosali F;Giudici F;Romagnani P;Parronchi P;Tonelli F;Maggi E;Romagnani S
通讯作者：
Romagnani S
人白细胞介素17产生的细胞起源于CD161+ CD4+ T细胞前体。
影响因子：
15.3
作者：
Cosmi, Lorenzo;De Palma, Raffaele;Santarlasci, Veronica;Maggi, Laura;Capone, Manuela;Frosali, Francesca;Rodolico, Gabriella;Querci, Valentina;Abbate, Gianfranco;Angeli, Roberta;Berrino, Liberato;Fambrini, Massimiliano;Caproni, Marzia;Tonelli, Francesco;Lazzeri, Elena;Parronchi, Paola;Liotta, Francesco;Maggi, Enrico;Romagnani, Sergio;Annunziato, Francesco
通讯作者：
Annunziato, Francesco
影响因子：
29.4
作者：
Feng T;Cao AT;Weaver CT;Elson CO;Cong Y
通讯作者：
Cong Y
影响因子：
30.5
作者：
通讯作者：
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