Activation of p38 MAPK in CD4 T cells controls IL-17 production and autoimmune encephalomyelitis
Activation of p38 MAPK in CD4 T cells controls IL-17 production and autoimmune encephalomyelitis
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DOI：
10.1182/blood-2011-02-336552
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发表时间：
2011-09-22
期刊：
影响因子：
20.3
通讯作者：
Teuscher, Cory
中科院分区：
文献类型：
--
作者：
Noubade, Rajkumar;Krementsov, Dimitry N.;Teuscher, Cory
尽管一些转录因子已被证明对CD4 Th细胞诱导和维持IL-17表达至关重要，但对非转录机制的作用知之甚少。在这里，我们通过激活真核翻译起始因子4E/MAPK相互作用激酶（eIF-4E/MNK）途径，通过调节CD4 T细胞中IL-17的合成，证明p38 MAPK信号通路对体外和体内IL-17的产生至关重要。我们还表明，p38 MAPK激活是慢性和复发缓解型实验性过敏性脑脊髓炎（EAE）的发生和进展所必需的，EAE是多发性硬化症的主要自身免疫性模型。此外，我们发现在T细胞中特异性调节p38 MAPK活性足以调节EAE的严重程度。因此，除基因表达调控外的其他机制也有助于Th17细胞效应功能，并可能参与其他Th17细胞介导的疾病的发病机制。(血。2011;118 (12):3290 - 3300)
Although several transcription factors have been shown to be critical for the induction and maintenance of IL-17 expression by CD4 Th cells, less is known about the role of nontranscriptional mechanisms. Here we show that the p38 MAPK signaling pathway is essential for in vitro and in vivo IL-17 production by regulating IL-17 synthesis in CD4 T cells through the activation of the eukaryotic translation initiation factor 4E/MAPK-interacting kinase (eIF-4E/MNK) pathway. We also show that p38 MAPK activation is required for the development and progression of both chronic and relapsing-remitting forms of experimental allergic encephalomyelitis (EAE), the principal autoimmune model of multiple sclerosis. Furthermore, we show that regulation of p38 MAPK activity specifically in T cells is sufficient to modulate EAE severity. Thus, mechanisms other than the regulation of gene expression also contribute to Th17 cell effector functions and, potentially, to the pathogenesis of other Th17 cell-mediated diseases. (Blood. 2011;118(12):3290-3300)