PDLIM2 restricts Th1 and Th17 differentiation and prevents autoimmune disease.
PDLIM2 restricts Th1 and Th17 differentiation and prevents autoimmune disease.
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DOI：
10.1186/2045-3701-2-23
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发表时间：
2012-06-25
影响因子：
7.5
通讯作者：
Xiao G
中科院分区：
文献类型：
--
作者：
Qu Z;Fu J;Ma H;Zhou J;Jin M;Mapara MY;Grusby MJ;Xiao G
PDLIM 2对炎性转录因子NF-κB和STAT的终止是必需的，但对免疫细胞和免疫组织/器官的发育是必需的。目前，PDLIM 2是否以及如何参与生理和致病过程仍不清楚。在这里，我们报告，幼稚PDLIM 2缺陷的CD 4 + T细胞倾向于分化为Th 1和Th 17细胞。然而，PDLIM 2缺陷对向Th 2或Treg细胞的谱系定型没有明显影响。值得注意的是，PDLIM 2缺陷型小鼠表现出对实验性自身免疫性脑炎（EAE）的易感性增加，EAE是一种Th 1和/或Th 17细胞介导的多发性硬化症（MS）炎性疾病模型。机制研究进一步表明PDLIM 2是限制Th 1和Th 17细胞因子表达所必需的，这与PDLIM 2在终止NF-κB和STAT激活中的作用一致。这些发现表明，PDLIM 2是T细胞介导的免疫应答的关键调节剂，其可被靶向用于治疗人类自身免疫性疾病。
PDLIM2 is essential for the termination of the inflammatory transcription factors NF-κB and STAT but is dispensable for the development of immune cells and immune tissues/organs. Currently, it remains unknown whether and how PDLIM2 is involved in physiologic and pathogenic processes. Here we report that naive PDLIM2 deficient CD4+ T cells were prone to differentiate into Th1 and Th17 cells. PDLIM2 deficiency, however, had no obvious effect on lineage commitment towards Th2 or Treg cells. Notably, PDLIM2 deficient mice exhibited increased susceptibility to experimental autoimmune encephalitis (EAE), a Th1 and/or Th17 cell-mediated inflammatory disease model of multiple sclerosis (MS). Mechanistic studies further indicate that PDLIM2 was required for restricting expression of Th1 and Th17 cytokines, which was in accordance with the role of PDLIM2 in the termination of NF-κB and STAT activation. These findings suggest that PDLIM2 is a key modulator of T-cell-mediated immune responses that may be targeted for the therapy of human autoimmune diseases.
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影响因子：
11.2
作者：
Qu Z;Yan P;Fu J;Jiang J;Grusby MJ;Smithgall TE;Xiao G
通讯作者：
Xiao G
影响因子：
4.4
作者：
Mathur, Anubhav N.;Chang, Hua-Chen;Kaplan, Mark H.
通讯作者：
Kaplan, Mark H.
DOI：
10.1073/pnas.0609914104
发表时间：
2007-03-27
影响因子：
11.1
作者：
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通讯作者：
Xiao, Gutian
影响因子：
32.4
作者：
Tanaka, T;Soriano, MA;Grusby, MJ
通讯作者：
Grusby, MJ
影响因子：
20.3
作者：
Yan, Pengrong;Fu, Jing;Xiao, Gutian
通讯作者：
Xiao, Gutian