STAT4 controls GM-CSF production by both Th1 and Th17 cells during EAE.
STAT4 controls GM-CSF production by both Th1 and Th17 cells during EAE.
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DOI：
10.1186/s12974-015-0351-3
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发表时间：
2015-06-30
影响因子：
9.3
通讯作者：
Harrington LE
中科院分区：
文献类型：
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作者：
McWilliams IL;Rajbhandari R;Nozell S;Benveniste E;Harrington LE
In experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis, mice genetically deficient in the transcription factor signal transducer and activator of transcription 4 (STAT4) are resistant to disease. In contrast, deletion or inhibition of the Th1-associated cytokines IL-12 or IFNγ which act upstream and downstream of STAT4, respectively, does not ameliorate disease. These discordant findings imply that STAT4 may act in a non-canonical role during EAE. Recently, STAT4 has been shown to regulate GM-CSF production by CD4 T cells and this cytokine is necessary for the induction of EAE. However, it is not known if STAT4 controls GM-CSF production by both Th1 and Th17 effector CD4 T cells. This study utilized the MOG35–55 peptide immunization model of EAE. Intracellular cytokine staining and novel mixed bone marrow chimeric mice were used to study the CD4 T cell-intrinsic role of STAT4 during disease. STAT4 chromatin-immunoprecipitation (ChIP-PCR) experiments were performed to show STAT4 directly interacts with the Csf2 gene loci. Herein, we demonstrate that STAT4 controls CD4 T cell-intrinsic GM-CSF production by both Th1 and Th17 CD4 T cells during EAE as well as in vitro. Importantly, we show that STAT4 interacts with the Csf2 locus in MOG35–55-activated effector CD4 T cells demonstrating direct modulation of GM-CSF. Overall, these studies illustrate a previously unrecognized role of STAT4 to regulate GM-CSF production by not only Th1 cells, but also Th17 effector CD4 T cell subsets during EAE pathogenesis. Critically, these data highlight for the first time that STAT4 is able to modulate the effector profile of Th17 CD4 T cell subsets, which redefines our current understanding of STAT4 as a Th1-centric factor. The online version of this article (doi:10.1186/s12974-015-0351-3) contains supplementary material, which is available to authorized users.
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DOI：
10.4049/jimmunol.1203229
发表时间：
2013-07-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Pham D;Yu Q;Walline CC;Muthukrishnan R;Blum JS;Kaplan MH
通讯作者：
Kaplan MH
DOI：
10.4049/jimmunol.181.8.5681
发表时间：
2008-10-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Mo C;Chearwae W;O'Malley JT;Adams SM;Kanakasabai S;Walline CC;Stritesky GL;Good SR;Perumal NB;Kaplan MH;Bright JJ
通讯作者：
Bright JJ
影响因子：
7
作者：
Becher B;Segal BM
通讯作者：
Segal BM
TH1对TH17：T细胞细胞因子在多发性硬化症中是否相关？
DOI：
10.1016/j.bbadis.2010.05.012
发表时间：
2011-02
影响因子：
6.2
作者：
Lovett-Racke, Amy E.;Yang, Yuhong;Racke, Michael K.
通讯作者：
Racke, Michael K.
影响因子：
30.5
作者：
通讯作者：
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