Inhibiting two pore channels by tetrandrine induces expansion of TNFR2+CD4+Foxp3+ regulatory T cells

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	Inhibiting two pore channels by tetrandrine induces expansion of TNFR2+CD4+Foxp3+ regulatory T cells
	He, T.; Yang, D.; Li, X.; Chen, S.; Chen, Y.; Chou, C.; Trivett, A.; Oppenheim, J; Chen, X.
	2020-09-30
Source Publication	Science Advances
ISSN	2375-2548
Pages	1-13
Abstract	Transmembrane TNF (tmTNF), preferentially binding to and activating TNFR2, stimulates the proliferative expansion of TNFR2+CD4+Foxp3+ regulatory T cells (Tregs). In this study, we found that tetrandrine (TET), a component of anti-inflammatory herbal medicine, markedly enhanced tmTNF expression on antigen presenting cells (APCs). Furthermore, co-culture of TET-treated dendritic cells (DCs) with CD4 cells or injection of TET into mice increased the number of Tregs in a TNF/TNFR2-dependent manner. In a mouse colitis model, expansion of Tregs induced by TET potently inhibited colon inflammation. TET is a well characterized two pore channels (TPCs) inhibitor and our subsequent study revealed that this property of TET was responsible for inhibiting the surface expression of TNF-alpha converting enzyme (TACE). Treatment with other TPCs inhibitors or TPCs siRNA also enhanced tmTNF expression by inhibiting TACE expression on plasma membrane. This effect of TPCs inhibitors may be therapeutically harnessed in the treatment of autoimmune diseases, allograft rejection and GvHD.
Keyword	tetrandrine Treg TNFR2
URL	View the original
Language	英語English
The Source to Article	PB_Publication
PUB ID	45319
Document Type	Journal article
Collection	University of Macau
Corresponding Author	Oppenheim, J; Chen, X.
Recommended Citation GB/T 7714	He, T.,Yang, D.,Li, X.,et al. Inhibiting two pore channels by tetrandrine induces expansion of TNFR2+CD4+Foxp3+ regulatory T cells[J]. Science Advances, 2020, 1-13.
APA	He, T.., Yang, D.., Li, X.., Chen, S.., Chen, Y.., Chou, C.., Trivett, A.., Oppenheim, J., & Chen, X. (2020). Inhibiting two pore channels by tetrandrine induces expansion of TNFR2+CD4+Foxp3+ regulatory T cells. Science Advances, 1-13.
MLA	He, T.,et al."Inhibiting two pore channels by tetrandrine induces expansion of TNFR2+CD4+Foxp3+ regulatory T cells".Science Advances (2020):1-13.

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