The p38 MAPK inhibitor SB203580 abrogates TNF-mediated expansion of regulatory T cells

UM > Institute of Chinese Medical Sciences

Status	已發表Published
	The p38 MAPK inhibitor SB203580 abrogates TNF-mediated expansion of regulatory T cells
	Chen, X.; He, T.Zh.
	2017-05-01
Source Publication	Journal of Immunology
Abstract	CD4+FoxP3+ regulatory T cells (Tregs) represent a major cellular mechanism of immune evasion of tumor. There is compelling evidence that TNF is able to activate and expand Tregs through TNFR2. However, it remains unclear which TNFR2 signaling pathway(s) is required for the activation of Tregs. In this study, we determined the identity of the TNFR2 signaling components by using specific small molecule inhibitors. To this end, MACS purified CD4+ T cells from WT C57BL/6 mice were labeled with CFSE and stimulated with TNF in the presence of IL-2. The proliferation of Tregs was analyzed by FACS, gating on FoxP3+cells. Treatment with the p38 MAPK inhibitor SB203580, rather than NF-κB inhibitors, abrogated TNF-mediated expansion of Tregs. In addition, administration of SB203580 blocked LPS-induced expansion of Tregs and up-regulation of TNFR2 expression on Tregs in vivo. Importantly, treatment with SB203580 potently inhibited lung metastasis of mouse 4T1 breast cancer, which presumably resulted from reduction of Treg activity in tumor bearing mice. Therefore, our data suggest that activation of p38 MAPK signaling pathway is required for TNF-mediated proliferative expansion of Tregs. Targeting p38 MAPK pathway may represent a novel strategy to enhance the efficacy of cancer immunotherapy through suppression of Treg activity.
Keyword	SB203580 small molecule inhibitors TNFR2 Tregs
URL	View the original
Language	英語English
The Source to Article	PB_Publication
PUB ID	31622
Document Type	Conference paper
Collection	Institute of Chinese Medical Sciences
Recommended Citation GB/T 7714	Chen, X.,He, T.Zh.. The p38 MAPK inhibitor SB203580 abrogates TNF-mediated expansion of regulatory T cells[C], 2017.
APA	Chen, X.., & He, T.Zh. (2017). The p38 MAPK inhibitor SB203580 abrogates TNF-mediated expansion of regulatory T cells. Journal of Immunology.

Files in This Item:
There are no files associated with this item.

If you have any objections to this item, please fill out the form below and the administrator will contact you as soon as possible.
Content:
Email：	*
Affiliation No.
Verification Code:	Refresh

Any comments and suggestions are welcomed.
Title:	*
Content:
Email：	*
Verification Code:	Refresh