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In vitro generated Th17 cells support the expansion and phenotypic stability of CD4+ Foxp3+ regulatory T cells in vivo
Qiong Zhou1; Ya Hu1; O.M. Zack Howard1; Joost J. Oppenheim1; Xin Chen2
2014-01
Source PublicationCYTOKINE
ISSN1043-4666
Volume65Issue:1Pages:56-64
Abstract

CD4+ T cells stimulate immune responses through distinct patterns of cytokine produced by Th1, Th2 or Th17 cells, or inhibit immune responses through Foxp3-expressing regulatory T cells (Tregs). Paradoxically, effector T cells were recently shown to activate Tregs, however, it remains unclear which Th subset is responsible for this effect. In this study, we found that Th17 cells expressed the highest levels of TNF among in vitro generated Th subsets, and most potently promoted expansion and stabilized Foxp3 expression by Tregs when co-transferred into Rag1−/− mice. Both TNF and IL-2 produced by Th17 cells contributed to this effect. The stimulatory effect of Th17 cells on Tregs was largely abolished when co-transferred with TNFR2-deficient Tregs. Furthermore, Tregs deficient in TNFR2 also supported a much lower production of IL-17A and TNF expression by co-transferred Th17 cells. Thus, our data indicate that the TNF-TNFR2 pathway plays a crucial role in the reciprocal stimulatory effect of Th17 cells and Tregs. This bidirectional interaction should be taken into account when designing therapy targeting Th17 cells, Tregs, TNF and TNFR2.

KeywordRegulatory t Cell Il-2 Tnf Tnfr2 Th17
DOIhttp://doi.org/10.1016/j.cyto.2013.09.008
Indexed BySCI
Language英语
WOS Research AreaBiochemistry & Molecular Biology ; Cell Biology ; Immunology
WOS SubjectBiochemistry & Molecular Biology ; Cell Biology ; Immunology
WOS IDWOS:000328716100009
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Cited Times [WOS]:12   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorXin Chen
Affiliation1.Laboratory of Molecular Immunoregulation; Cancer Inflammation Program, Center for Cancer Research, NCI
2.Basic Science Program, SAIC-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland 21702, United States
Recommended Citation
GB/T 7714
Qiong Zhou,Ya Hu,O.M. Zack Howard,et al. In vitro generated Th17 cells support the expansion and phenotypic stability of CD4+ Foxp3+ regulatory T cells in vivo[J]. CYTOKINE,2014,65(1):56-64.
APA Qiong Zhou,Ya Hu,O.M. Zack Howard,Joost J. Oppenheim,&Xin Chen.(2014).In vitro generated Th17 cells support the expansion and phenotypic stability of CD4+ Foxp3+ regulatory T cells in vivo.CYTOKINE,65(1),56-64.
MLA Qiong Zhou,et al."In vitro generated Th17 cells support the expansion and phenotypic stability of CD4+ Foxp3+ regulatory T cells in vivo".CYTOKINE 65.1(2014):56-64.
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