IL-2 and IL-4 stimulate MEK1 expression and contribute to T cell resistance against suppression by TGF-beta and IL-10 in asthma.
IL-2 and IL-4 stimulate MEK1 expression and contribute to T cell resistance against suppression by TGF-beta and IL-10 in asthma.
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DOI：
10.4049/jimmunol.1000690
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发表时间：
2010-11-15
期刊：
影响因子：
--
通讯作者：
Alam R
中科院分区：
文献类型：
--
作者：
Liang Q;Guo L;Gogate S;Karim Z;Hanifi A;Leung DY;Gorska MM;Alam R
The T cell-driven airway inflammation in chronic asthma is uninhibited and sustained. We examined the resistance of T cells from asthmatic patients against suppression by TGF-β, IL-10 and glucocorticoids and explored its signaling mechanism. CD4+CD25− T cells from allergic asthmatic subjects demonstrated increased TCR-stimulated proliferation as compared with healthy and chronic obstructive pulmonary disease controls. This proliferation was resistant to inhibition by TGF-β, IL-10, and dexamethasone and to anergy induction. CD4 T cells from asthmatic patients, but not chronic obstructive pulmonary disease, allergic rhinitis, and healthy subjects, showed increased expression of MEK1, heightened phosphorylation of ERK1/2, and increased levels of c-Fos. IL-2 and IL-4 stimulated the expression of MEK1 and c-Fos and induced T cell resistance. The inhibition of MEK1 reversed, whereas induced expression of c-Fos and JunB promoted T cell resistance against TGF-β– and IL-10–mediated suppression. We have uncovered an IL-2– and IL-4–driven MEK1 induction mechanism that results in heightened ERK1/2 activation in asthmatic T cells and make them resistant to certain inhibitory mechanisms.
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CD4+ CD25+调节T细胞体内转移后气道炎症和过度反应性的分辨率取决于白介素10。
DOI：
10.1084/jem.20051166
发表时间：
2005-12-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1084/jem.20030589
发表时间：
2004-02-02
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Gorska MM;Stafford SJ;Cen O;Sur S;Alam R
通讯作者：
Alam R
影响因子：
14.2
作者：
Bellinghausen, I;Klostermann, B;Saloga, J
通讯作者：
Saloga, J
影响因子：
14.2
作者：
Jartti, Tuomas;Burmeister, Kristjan A.;Gern, James E.
通讯作者：
Gern, James E.
影响因子：
14.2
作者：
Gernez, Yael;Tirouvanziam, Rabindra;Nadeau, Kari C.
通讯作者：
Nadeau, Kari C.