Zinc suppresses Th17 development via inhibition of STAT3 activation
Zinc suppresses Th17 development via inhibition of STAT3 activation
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DOI：
10.1093/intimm/dxq017
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发表时间：
2010-05-01
影响因子：
4.4
通讯作者：
Hirano, Toshio
中科院分区：
文献类型：
--
作者：
Kitabayashi, Chika;Fukada, Toshiyuki;Hirano, Toshio
锌（Zn）是许多酶和转录因子活性或维持其结构所需的必需微量金属。锌在免疫反应和炎症中具有多种作用，尽管锌如何在分子基础上影响这些反应还不清楚。我们在这里发现，锌抑制T（h）17介导的自身免疫性疾病，至少部分通过抑制T（h）17细胞的发展，通过减弱STAT 3激活。在注射II型胶原蛋白诱导关节炎的小鼠中，锌治疗抑制了T（h）17细胞的发育。锌抑制IL-6介导的STAT 3活化和T（h）17细胞体外发育。重要的是，锌结合改变了STAT 3的α-螺旋二级结构，破坏了STAT 3与JAK 2激酶和磷酸肽的结合，该磷酸肽包括来自IL-6信号转导蛋白gp 130的STAT 3结合基序。因此，我们得出结论，锌抑制STAT 3激活，这是T（h）17发育的关键步骤。
Zinc (Zn) is an essential trace metal required by many enzymes and transcription factors for their activity or the maintenance of their structure. Zn has a variety of effects in the immune responses and inflammation, although it has not been well known how Zn affects these reactions on the molecular basis. We here showed that Zn suppresses T(h)17-mediated autoimmune diseases at lest in part by inhibiting the development of T(h)17 cells via attenuating STAT3 activation. In mice injected with type II collagen to induce arthritis, Zn treatment inhibited T(h)17 cell development. IL-6-mediated activation of STAT3 and in vitro T(h)17 cell development were all suppressed by Zn. Importantly, Zn binding changed the alpha-helical secondary structure of STAT3, disrupting the association of STAT3 with JAK2 kinase and with a phospho-peptide that included a STAT3-binding motif from the IL-6 signal transducer gp130. Thus, we conclude that Zn suppresses STAT3 activation, which is a critical step for T(h)17 development.