TNFR2 expression by CD4 effector T cells is required to induce full-fledged experimental colitis.
TNFR2 expression by CD4 effector T cells is required to induce full-fledged experimental colitis.
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CD4 效应 T 细胞表达 TNFR2 是诱导成熟的实验性结肠炎所必需的。
DOI：
10.1038/srep32834
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发表时间：
2016-09-07
影响因子：
4.6
通讯作者：
Oppenheim JJ
中科院分区：
文献类型：
--
作者：
Chen X;Nie Y;Xiao H;Bian Z;Scarzello AJ;Song NY;Trivett AL;Yang D;Oppenheim JJ
现在有令人信服的证据表明，TNFR 2在CD 4 + Foxp 3+调节性T细胞（Tcells）上组成型表达，并且TNF-TNFR 2相互作用对于Tcells的活化、扩增和功能稳定性至关重要。然而，我们发现，在TCR刺激后，CD 4 + Foxp 3 −效应T细胞（Teffs）上TNFR 2的表达也上调。为了确定TNFR 2在致病性CD 4 T细胞中的作用，我们比较了将来自WT小鼠和TNFR 2 −/−小鼠的幼稚CD 4细胞转移到Rag 1−/−受体中的效果。与WT Teff不同，TNFR 2缺陷型Teff细胞的转移未能诱导完全成熟的结肠炎。这是由于TNFR 2缺陷Teff细胞在淋巴细胞减少小鼠中的增殖性扩增缺陷，以及它们在每个细胞基础上表达促炎性Th 1细胞因子的能力降低。在体外，TNFR 2缺陷型幼稚CD 4细胞对抗CD 3刺激的增殖反应与WT幼稚CD 4细胞相比显著降低。TNFR 2缺陷型Teff细胞对TCR刺激的低增殖反应与p100/p52比率增加相关，为我们的研究结果提供了机制基础。因此，该研究清楚地表明TNFR 2对于致病性Teff细胞的增殖扩增是重要的。
There is now compelling evidence that TNFR2 is constitutively expressed on CD4+ Foxp3+ regulatory T cells (Tregs) and TNF-TNFR2 interaction is critical for the activation, expansion and functional stability of Tregs. However, we showed that the expression of TNFR2 was also up-regulated on CD4+ Foxp3− effector T cells (Teffs) upon TCR stimulation. In order to define the role of TNFR2 in the pathogenic CD4 T cells, we compared the effect of transferred naïve CD4 cells from WT mice and TNFR2−/− mice into Rag 1−/− recipients. Transfer of TNFR2-deficient Teff cells failed to induce full-fledged colitis, unlike WT Teffs. This was due to defective proliferative expansion of TNFR2-deficient Teff cells in the lymphopenic mice, as well as their reduced capacity to express proinflammatory Th1 cytokine on a per cell basis. In vitro, the proliferative response of TNFR2 deficient naïve CD4 cells to anti-CD3 stimulation was markedly decreased as compared with that of WT naïve CD4 cells. The hypoproliferative response of TNFR2-deficient Teff cells to TCR stimulation was associated with an increased ratio of p100/p52, providing a mechanistic basis for our findings. Therefore, this study clearly indicates that TNFR2 is important for the proliferative expansion of pathogenic Teff cells.
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影响因子：
5.4
作者：
Chen, Xin;Subleski, Jeffrey J.;Hamano, Ryoko;Howard, O. M. Zack;Wiltrout, Robert H.;Oppenheim, Joost J.
通讯作者：
Oppenheim, Joost J.
影响因子：
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影响因子：
15.3
作者：
Asseman, C;Mauze, S;Leach, M W;Coffman, R L;Powrie, F
通讯作者：
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影响因子：
5.5
作者：
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通讯作者：
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