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TNF optimally activatives regulatory T cells by inducing TNF receptor superfamily members TNFR2, 4‐1BB and OX40
Ryoko Hamano1,4; Jiaqiang Huang2; Teizo Yoshimura1; Joost J. Oppenheim1; Xin Chen3
2011-07
Source PublicationEUROPEAN JOURNAL OF IMMUNOLOGY
ISSN0014-2980
Volume41Issue:7Pages:2010-2020
Abstract

TNF is a pleiotropic cytokine with intriguing biphasic pro-inflammatory and anti-inflammatory effects. Our previous studies demonstrated that TNF up-regulated FoxP3 expression and activated and expanded CD4+FoxP3+ regulatory T cells (Tregs) by utilizing TNFR2. Further, TNFR2- expressing Tregs exhibited maximal suppressive activity. In this study, we show that TNF, in concert with IL-2, preferentially up-regulated mRNA and surface expression of TNFR2, 4-1BB and OX40 on Tregs. Agonistic antibodies against 4-1BB and OX40 also induced the proliferation of suppressive Tregs. Thus, TNF amplifies its stimulatory effect on Tregs by inducing TNF receptor superfamily (TNFRSF) members. In addition, administration of neutralizing anti-TNF Ab blocked LPS-induced expansion of splenic Tregs and up-regulation of TNFR2, OX40 and 4-1BB receptors on Tregs in vivo, indicating that the expansion of Tregs expressing these co-stimulatory TNFRSF members in response to LPS is mediated by TNF. Taken together, our novel data indicate that TNF preferentially up-regulates TNFR2 on Tregs, and this is amplified by the stimulation of 4-1BB and OX40, resulting in the optimal activation of Tregs and augmented attenuation of excessive inflammatory responses.

KeywordTnf Regulatory t Cells Co-stimulation Immune Regulation
DOIhttp://doi.org/10.1002/eji.201041205
Indexed BySCI
Language英语
WOS Research AreaImmunology
WOS SubjectImmunology
WOS IDWOS:000293131200022
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Cited Times [WOS]:53   [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-Frederick, Frederick, Maryland 21702-1201
2.SABiosciences Corporation, A QIAGEN Company, Frederick, MD 21703
3.Basic Science Program, SAIC-Frederick, Inc., NCI-Frederick
4.Division of Rheumatology, Department of Internal Medicine, Kanazawa University Graduate School of Medicine, Kanazawa, Ishikawa, Japan
Recommended Citation
GB/T 7714
Ryoko Hamano,Jiaqiang Huang,Teizo Yoshimura,et al. TNF optimally activatives regulatory T cells by inducing TNF receptor superfamily members TNFR2, 4‐1BB and OX40[J]. EUROPEAN JOURNAL OF IMMUNOLOGY,2011,41(7):2010-2020.
APA Ryoko Hamano,Jiaqiang Huang,Teizo Yoshimura,Joost J. Oppenheim,&Xin Chen.(2011).TNF optimally activatives regulatory T cells by inducing TNF receptor superfamily members TNFR2, 4‐1BB and OX40.EUROPEAN JOURNAL OF IMMUNOLOGY,41(7),2010-2020.
MLA Ryoko Hamano,et al."TNF optimally activatives regulatory T cells by inducing TNF receptor superfamily members TNFR2, 4‐1BB and OX40".EUROPEAN JOURNAL OF IMMUNOLOGY 41.7(2011):2010-2020.
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