Ablation of tumor progression locus 2 promotes a type 2 Th cell response in Ovalbumin-immunized mice.
Ablation of tumor progression locus 2 promotes a type 2 Th cell response in Ovalbumin-immunized mice.
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DOI：
10.4049/jimmunol.0803730
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发表时间：
2010-01-01
期刊：
影响因子：
--
通讯作者：
Tsichlis PN
中科院分区：
文献类型：
--
作者：
Watford WT;Wang CC;Tsatsanis C;Mielke LA;Eliopoulos AG;Daskalakis C;Charles N;Odom S;Rivera J;O'Shea J;Tsichlis PN
The protein kinase encoded by the Tpl2 proto-oncogene regulates ERK activation and cytokine gene expression in macrophages in response to LPS and TNF-. In this study we show that OVA-immunized Tpl2−/− mice express high levels of IgE and develop more severe bronchoalveolar eosinophilic inflammation than Tpl2+/+ controls, when challenged with OVA intranasally. Bronchoalveolar exudates and supernatants of OVA-stimulated splenocytes from immunized Tpl2−/− mice express elevated levels of IL-4 and IL-5, suggesting that Tpl2 ablation promotes the Th2 polarization of the T cell response. Anti-CD3 stimulation of CD4+ T cells of wild-type and Tpl2 knockout mice revealed that Tpl2 ablation gives rise to a cell autonomous T cell defect that is primarily responsible for the Th2 polarization of the T cell response to Ag. This observation was further supported by experiments addressing the expression of Th1 and Th2 cytokines in OVA-stimulated mixed cultures of CD4+ T cells from Tpl2+/+/OT2 or Tpl2−/−/OT2 mice and dendritic cells from Tpl2+/+ or Tpl2−/− mice. Further studies revealed that Th1 cells express significantly higher levels of Tpl2 than Th2 cells. As a result, Tpl2−/− Th1 cells exhibit a stronger defect in ERK activation by anti-CD3 than Th2 cells and express low levels of T-bet. Given that the development of Th1 and Th2 cells depends on positive feedback signals from the T cells, themselves, the functional defect of the Tpl2−/− Th1 cells provides a mechanistic explanation for the T cell autonomous Th2 polarization in Tpl2−/− mice.
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影响因子：
11.2
作者：
Hatziapostolou, Maria;Polytarchou, Christos;Tsichlis, Philip N.
通讯作者：
Tsichlis, Philip N.
白介素5缺乏消除小鼠哮喘模型中的嗜酸性粒细胞，气道高反应性和肺损伤。
影响因子：
15.3
作者：
Foster, PS;Hogan, SP;Ramsay, AJ;Matthaei, KI;Young, IG
通讯作者：
Young, IG
影响因子：
24.3
作者：
Cruse, G;Kaur, D;Bradding, P
通讯作者：
Bradding, P
DOI：
10.1164/ajrccm/147.3.540
发表时间：
1993-03-01
期刊：
AMERICAN REVIEW OF RESPIRATORY DISEASE
影响因子：
--
作者：
CORRIGAN, CJ;HACZKU, A;KAY, AB
通讯作者：
KAY, AB
影响因子：
64.8
作者：
Belich, MP;Salmerón, A;Ley, SC
通讯作者：
Ley, SC