Status | 已發表Published |
Tetrandrine (TET) up-regulated mTNF expression on dendritic cells and consequently induces TNFR2 mediated proliferation of Tregs | |
He, T; Yang, D; Chen, X; Oppenheim, J | |
2018-05-01 | |
Source Publication | The Journal of Immunology |
Pages | 47.19-null |
Abstract | Tetrandrine (TET) is a chemical component derived from the Stephania Tetrandra, a traditional Chinese medicine with anti-inflammatory and immunosuppressive properties. The underlying mechanism of its immunosuppressive effect remains incompletely understood. There is now compelling evidence that CD4+Foxp3+ regulatory T cells (Tregs) play an indispensable role in the maintenance of immune homeostasis by actively suppressing the activation of effector immune cells. It is also established that TNF preferentially activates and expands Tregs through TNFR2. Therefore, we examined the effect of TET on TNF expression on dendritic cells (DCs) and its effect on Tregs in wildtype and TNFR2 KO mice. We found that, TET didn’t directly expand Tregs in vitro. But TET can increase TNF expression on mouse DC 2.4 cells and human monocyte-derived DCs with or without LPS stimulation in vitro. In addition, these effects of TET were not based on LPS contamination. Intraperitoneal (i.p.) injection of TET into wildtype and TNFR2 KO mice, TET treatment increased the number of functional suppressive Tregs which increased to ~1.5-fold compared with control mice. TNFR2 expression on Tregs rather than Teffs was up-regulated by TET treatment. However, the number of Tregs can’t be changed by TET in TNFR2 KO mice. Taken together, our study revealed that TET had the capacity to promote TNF expression on DCs and consequently to expand Tregs via TNF-TNFR2 signaling. Therefore, TNF-TNFR2 interaction network between DCs and Tregs represent a novel mechanism underlying the anti-inflammatory effect of this Chinese herb-derived naturally occurring compound. This work was supported by grants from the Macau Science and Technology Development Fund (FDCT) research grant 014/2015/A1 to X Chen and University of Macau research grant MYRG2016-00023-ICMS-QRCM and MYRG2017-00120-ICMS to X Chen. |
Keyword | TNFR2 CT26 cancer knockout |
URL | View the original |
Language | 英語English |
The Source to Article | PB_Publication |
PUB ID | 40806 |
Document Type | Conference paper |
Collection | Institute of Chinese Medical Sciences |
Recommended Citation GB/T 7714 | He, T,Yang, D,Chen, X,et al. Tetrandrine (TET) up-regulated mTNF expression on dendritic cells and consequently induces TNFR2 mediated proliferation of Tregs[C], 2018, 47.19-null. |
APA | He, T., Yang, D., Chen, X., & Oppenheim, J (2018). Tetrandrine (TET) up-regulated mTNF expression on dendritic cells and consequently induces TNFR2 mediated proliferation of Tregs. The Journal of Immunology, 47.19-null. |
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