Transcription factors early growth response gene (Egr) 2 and 3 control inflammatory responses of tolerant T cells.
Transcription factors early growth response gene (Egr) 2 and 3 control inflammatory responses of tolerant T cells.
复制标题
DOI：
10.1002/iid3.210
复制
发表时间：
2018-06
期刊：
影响因子：
--
通讯作者：
Wang P
中科院分区：
文献类型：
--
作者：
Omodho B;Miao T;Symonds ALJ;Singh R;Li S;Wang P
增殖受损和il - 2的产生是实验性T细胞耐受的标志。然而，在大多数自身免疫性疾病中，自身反应性T细胞并不表现为过度增殖，而是表现为炎症表型。我们现在已经证明转录因子Egr2和3对控制耐受性T细胞产生炎症细胞因子很重要，但对耐受性诱导不重要。在缺乏Egr2和3的情况下，T细胞的耐受性（通过受损的增殖和IL2的产生来衡量）仍然可以被诱导，但耐受性T细胞产生高水平的炎症细胞因子。Egr2和3调节分化抑制因子的表达，直接抑制T细胞的T - bet功能。事实上，在耐受条件下，Egr2/3缺陷T细胞中分化抑制因子如Id3和Tcf1的表达减少，炎症转录因子如RORγt和Bhlhe40的表达增加。此外，T - bet在耐受性T细胞中与Egr2共表达，Egr2/3缺陷导致耐受性T细胞中产生高水平的IFNγ。我们的研究结果表明，尽管增殖和IL2产生受损，但耐受T细胞在抗原刺激下可以表现出炎症反应，这至少部分由Egr2和3控制。
Impaired proliferation and production of IL2 are the hallmarks of experimental T cell tolerance. However, in most autoimmune diseases, auto‐reactive T cells do not display hyper proliferation, but inflammatory phenotypes. We have now demonstrated that the transcription factors Egr2 and 3 are important for the control of inflammatory cytokine production by tolerant T cells, but not for tolerance induction. In the absence of Egr2 and 3, T cell tolerance, as measured by impaired proliferation and production of IL2, can still be induced, but tolerant T cells produced high levels of inflammatory cytokines. Egr2 and 3 regulate expression of differentiation repressors and directly inhibit T‐bet function in T cells. Indeed, decreased expression of differentiation repressors, such as Id3 and Tcf1, and increased expression of inflammatory transcription factors, such as RORγt and Bhlhe40 were found in Egr2/3 deficient T cells under tolerogenic conditions. In addition, T‐bet was co‐expressed with Egr2 in tolerant T cells and Egr2/3 defects leads to production of high levels of IFNγ in tolerant T cells. Our findings demonstrated that despite impaired proliferation and IL2 production, tolerant T cells can display inflammatory responses in response to antigen stimulation and this is controlled at least partly by Egr2 and 3.
登录
查看更多内容
DOI：
10.1084/jem.20160553
发表时间：
2017-06-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Miao T;Symonds ALJ;Singh R;Symonds JD;Ogbe A;Omodho B;Zhu B;Li S;Wang P
通讯作者：
Wang P
影响因子：
5.4
作者：
Anderson, Per O;Manzo, Barbara A;Sundstedt, Anette;Minaee, Sophie;Symonds, Alistair;Khalid, Sabah;Rodriguez-Cabezas, Maria E;Nicolson, Kirsty;Li, Suling;Wraith, David C;Wang, Ping
通讯作者：
Wang, Ping
影响因子：
29.7
作者：
Josefowicz SZ;Lu LF;Rudensky AY
通讯作者：
Rudensky AY
影响因子：
3.7
作者：
Ramon, Hilda E.;Cejas, Pedro J.;Turka, Laurence A.
通讯作者：
Turka, Laurence A.
影响因子：
100.3
作者：
Sakaguchi, Shimon;Vignali, Dario A. A.;Waldmann, Herman
通讯作者：
Waldmann, Herman