Bcl6 promotes follicular helper T-cell differentiation and PD-1 expression in a Blimp1-independent manner in mice.
Bcl6 promotes follicular helper T-cell differentiation and PD-1 expression in a Blimp1-independent manner in mice.
复制标题
DOI：
10.1002/eji.201747034
复制
发表时间：
2017-07
影响因子：
5.4
通讯作者：
Dent AL
中科院分区：
文献类型：
--
作者：
Xie MM;Koh BH;Hollister K;Wu H;Sun J;Kaplan MH;Dent AL
转录因子Bcl 6和Blimp 1在滤泡辅助性T（TFH）细胞的发育中具有相反的作用：Bcl 6促进和Blimp 1抑制TFH细胞分化。类似地，Bcl 6激活而Blimp 1抑制TFH细胞标志物PD-1的表达。然而，Bcl 6和Blimp 1抑制彼此的表达，使调控网络的解释复杂化。在这里，我们试图澄清Bcl 6和Blimp 1独立控制TFH细胞分化的程度，通过产生T细胞特异性缺失Bcl 6和Blimp 1的小鼠（双条件KO [dcKO]小鼠）。我们的数据表明，Blimp 1不控制TFH细胞分化的Bcl 6独立。然而，在dcKO小鼠中，T滤泡调节（TFR）细胞的群体独立于Bcl 6而发展。我们接下来分析了IL-10和PD-1的调节，这两个基因由Bcl 6和Blimp 1控制，并观察到Bcl 6独立于Blimp 1调节这两个基因。我们发现Bcl 6通过抑制Tbet/Tbx 21抑制Pdcd 1转录的能力而正调控PD-1表达。我们的数据显示了一种新的机制，积极控制基因表达的Bcl 6，并阐明如何Bcl 6和Blimp 1控制TFH细胞分化。
The transcription factors Bcl6 and Blimp1 have opposing roles in the development of the follicular helper T (TFH) cells: Bcl6 promotes and Blimp1 inhibits TFH cell differentiation. Similarly, Bcl6 activates, while Blimp1 represses, expression of the TFH cell marker PD-1. However, Bcl6 and Blimp1 repress each other’s expression, complicating the interpretation of the regulatory network. Here we sought to clarify the extent to which Bcl6 and Blimp1 independently control TFH cell differentiation by generating mice with T cell specific deletion of both Bcl6 and Blimp1 (double conditional KO [dcKO] mice). Our data indicate that Blimp1 does not control TFH cell differentiation independently of Bcl6. However, a population of T follicular regulatory (TFR) cells developed independently of Bcl6 in dcKO mice. We next analyzed regulation of IL-10 and PD-1, two genes controlled by both Bcl6 and Blimp1, and observed that Bcl6 regulates both genes independently of Blimp1. We found Bcl6 positively regulates PD-1 expression by inhibiting the ability of Tbet/Tbx21 to repress Pdcd1 transcription. Our data show a novel mechanism for positive control of gene expression by Bcl6, and illuminate how Bcl6 and Blimp1 control TFH cell differentiation.
登录
查看更多内容
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
DOI：
10.1126/science.1176676
发表时间：
2009-08-21
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Nurieva RI;Chung Y;Martinez GJ;Yang XO;Tanaka S;Matskevitch TD;Wang YH;Dong C
通讯作者：
Dong C
DOI：
10.4049/jimmunol.1203229
发表时间：
2013-07-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Pham D;Yu Q;Walline CC;Muthukrishnan R;Blum JS;Kaplan MH
通讯作者：
Kaplan MH
DOI：
10.1084/jem.20141380
发表时间：
2015-04-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hatzi K;Nance JP;Kroenke MA;Bothwell M;Haddad EK;Melnick A;Crotty S
通讯作者：
Crotty S
影响因子：
4.4
作者：
Wollenberg, Ivonne;Agua-Doce, Ana;Graca, Luis
通讯作者：
Graca, Luis