STAT1-activating cytokines limit Th17 responses through both T-bet-dependent and -independent mechanisms.
STAT1-activating cytokines limit Th17 responses through both T-bet-dependent and -independent mechanisms.
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DOI：
10.4049/jimmunol.1001343
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发表时间：
2010-12-01
期刊：
影响因子：
--
通讯作者：
Abbas AK
中科院分区：
文献类型：
--
作者：
Villarino AV;Gallo E;Abbas AK
Given the association with autoimmune disease, there is great interest in defining cellular factors that limit overactive or misdirected Th17-type inflammation. Using in vivo and in vitro models, we investigated the molecular mechanisms for cytokine-mediated inhibition of Th17 responses, focusing on the role of STAT1 and T-bet in this process. These studies demonstrate that, during systemic inflammation, STAT1- and T-bet-deficient T cells each exhibit a hyper-Th17 phenotype relative to WT controls. However, IL-17 production was higher in the absence of T-bet and, when both STAT1 and T-bet were deleted, there was no further increase, with the double-deficient cells instead behaving more like STAT1-deficient counterparts. Similar trends were observed during in vitro priming, with production of Th17-type cytokines higher in T-bet−/− T cells than in either STAT1−/− or STAT1−/− T-bet−/− counterparts. The ability of IFN-γ and IL-27 to suppress Th17 responses was reduced in T-bet-deficient cells and, most importantly, ectopic T-bet could suppress signature Th17 gene products, including IL-17A, IL-17F, IL-22 and RORγT, even in STAT1-deficient T cells. Taken together, these studies formally establish that, downstream of IFN-γ, IL-27 and likely all STAT1-activating cytokines, there are both STAT1 and T-bet-dependent pathways capable of suppressing Th17 responses.
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影响因子：
64.5
作者：
Ivanov, Ivaylo I.;McKenzie, Brent S.;Littman, Dan R.
通讯作者：
Littman, Dan R.
T-BET的丧失，但不是STAT1阻止了实验性自身免疫性脑脊髓炎的发展。
影响因子：
15.3
作者：
Bettelli, E;Sullivan, B;Szabo, SJ;Sobel, RA;Glimcher, H;Kuchroo, VK
通讯作者：
Kuchroo, VK
影响因子：
4.4
作者：
Diveu, Caroline;McGeachy, Mandy J.;Kastelein, Robert A.
通讯作者：
Kastelein, Robert A.
影响因子：
4.4
作者：
Liao, Jia-Jun;Huang, Mei-Chuan;Goetzl, Edward J.
通讯作者：
Goetzl, Edward J.
影响因子：
56.9
作者：
Hwang, ES;Szabo, SJ;Glimcher, LH
通讯作者：
Glimcher, LH