TGF-β signaling via Smad4 drives IL-10 production in effector Th1 cells and reduces T-cell trafficking in EAE.
TGF-β signaling via Smad4 drives IL-10 production in effector Th1 cells and reduces T-cell trafficking in EAE.
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DOI：
10.1002/eji.201141666
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发表时间：
2011-10
影响因子：
5.4
通讯作者：
Lovett-Racke, Amy E.
中科院分区：
文献类型：
--
作者：
Huss, David J.;Winger, Ryan C.;Cox, Gina Mavrikis;Guerau-De-Arellano, Mireia;Yang, Yuhong;Racke, Michael K.;Lovett-Racke, Amy E.
Effector Th1 cells perpetuate inflammatory damage in a number of autoimmune diseases, including MS and its animal model EAE. Recently, a self-regulatory mechanism was described where effector Th1 cells produce the immunomodulatory cytokine IL-10 to dampen the inflammatory response in both normal and autoimmune inflammation. While the presence of TGF-β has been suggested to enhance and stabilize an IFN-γ+IL-10+ phenotype, the molecular mechanism is poorly understood. Additionally, in the context of adoptive transfer EAE, it is unclear if IL-10 acts on the transferred Th1 cells or on cells within the host. In the present study, using myelinspecific TCR-Tg mice, repetitive Ag stimulation of effector Th1 cells in the presence of TGF-β increased the population of IFN-γ+IL-10+ cells, which correlated with a decrease in EAE severity. Additionally, TGF-β signaling caused binding of smad4 to the IL-10 promoter, providing molecular evidence for TGF-β-mediated IL-10 production from Th1 effector cells. Lastly, this study demonstrates that IL-10 reduced encephalitogenic markers such as IFN-γ and T-bet on Th1 effector cells expressing the IL-10R, but also prevented recruitment of both transferred and host-derived inflammatory T cells. These data establish a regulatory mechanism by which highly activated Th1 effector cells modulate their pathogenicity through induction of IL-10.
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DOI：
10.4049/jimmunol.1000288
发表时间：
2010-05-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Huss DJ;Winger RC;Peng H;Yang Y;Racke MK;Lovett-Racke AE
通讯作者：
Lovett-Racke AE
影响因子：
--
作者：
Bar-Or, Amit;Vollmer, Timothy;Garren, Hideki
通讯作者：
Garren, Hideki
影响因子：
3
作者：
BOS, JD;HAGENAARS, C;KAPSENBERG, ML
通讯作者：
KAPSENBERG, ML
DOI：
10.1073/pnas.0404887101
发表时间：
2004-10-05
影响因子：
11.1
作者：
Arnon, R;Aharoni, R
通讯作者：
Aharoni, R
DOI：
10.1073/pnas.0914500107
发表时间：
2010-02-16
影响因子：
11.1
作者：
Brooks, David G.;Walsh, Kevin B.;Oldstone, Michael B. A.
通讯作者：
Oldstone, Michael B. A.