Control of the inheritance of regulatory T cell identity by a cis element in the Foxp3 locus.
Control of the inheritance of regulatory T cell identity by a cis element in the Foxp3 locus.
复制标题
控制FOXP3基因座中的顺式元素对调节T细胞身份的遗传控制。
DOI：
10.1016/j.cell.2014.07.031
复制
发表时间：
2014-08-14
期刊：
影响因子：
64.5
通讯作者：
Rudensky AY
中科院分区：
文献类型：
--
作者：
Feng Y;Arvey A;Chinen T;van der Veeken J;Gasteiger G;Rudensky AY
在多细胞生物体中，专门的功能被委托给不同的细胞类型，其身份和功能完整性在挑战时得以保持。然而，很少有人知道的机制，使谱系遗传及其生物学意义。表达转录因子Foxp 3的调节性T（Treg）细胞在动物的整个生命周期中抑制致命的自身免疫。在这里，我们表明，一个专门的Foxp 3内含子元件CNS 2保持Treg细胞谱系的身份，作为一个传感器的必要的Treg细胞生长因子IL-2和其下游目标STAT 5。当IL-2受限时，CNS 2在成熟Treg细胞分裂期间维持Foxp 3表达，并抵消导致Foxp 3损失的促炎细胞因子信号传导。CNS 2介导的Foxp 3表达的稳定遗传对于Treg细胞充分抑制不同类型的慢性炎症并防止其分化为炎性效应细胞至关重要。所描述的机制可以代表分化细胞状态遗传的一般原理。
In multicellular organisms, specialized functions are delegated to distinct cell types whose identity and functional integrity is maintained upon challenge. However, little is known about the mechanisms enabling lineage inheritance and their biological implications. Regulatory T (Treg) cells, which express the transcription factor Foxp3, suppress fatal autoimmunity throughout the lifespan of animals. Here, we show that a dedicated Foxp3 intronic element CNS2 maintains Treg cell lineage identity by acting as a sensor of the essential Treg cell growth factor IL-2 and its downstream target STAT5. CNS2 sustains Foxp3 expression during division of mature Treg cells when IL-2 is limiting and counteracts pro-inflammatory cytokine signaling that leads to the loss of Foxp3. CNS2 mediated stable inheritance of Foxp3 expression is critical for adequate suppression of diverse types of chronic inflammation by Treg cells and prevents their differentiation into inflammatory effector cells. The described mechanism may represent a general principle of the inheritance of differentiated cell states.
登录
查看更多内容
影响因子：
32.4
作者：
Bailey-Bucktrout, Samantha L.;Martinez-Llordella, Marc;Zhou, Xuyu;Anthony, Bryan;Rosenthal, Wendy;Luche, Herve;Fehling, Hans J.;Bluestone, Jeffrey A.
通讯作者：
Bluestone, Jeffrey A.
DOI：
10.4049/jimmunol.1301892
发表时间：
2014-01-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Ogawa C;Tone Y;Tsuda M;Peter C;Waldmann H;Tone M
通讯作者：
Tone M
影响因子：
29.7
作者：
Josefowicz SZ;Lu LF;Rudensky AY
通讯作者：
Rudensky AY
影响因子：
9.2
作者：
Mullen, AC;Hutchins, AS;Reiner, SL
通讯作者：
Reiner, SL
DOI：
10.1073/pnas.0811556106
发表时间：
2009-02-10
影响因子：
11.1
作者：
Komatsu, Noriko;Mariotti-Ferrandiz, Maria Encarnita;Hori, Shohei
通讯作者：
Hori, Shohei