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TNFR2 Is Critical for the Stabilization of the CD4+ Foxp3+ Regulatory T Cell Phenotype in the Inflammatory Environment
Xin Chen1; Xueqing Wu2; Qiong Zhou2; O.M. Zack Howard2; Mihai G. Netea3; Joost J. Oppenheim2
2013-02
Source PublicationJOURNAL OF IMMUNOLOGY
ISSN0022-1767
Volume190Issue:3Pages:1076-1084
Abstract

Several lines of evidence indicate the instability of CD4+FoxP3+ regulatory T cells (Tregs). We have therefore investigated means of promoting the stability of Tregs. In this study, we found that the proportion of Tregs in mouse strains deficient in TNFR2 or its ligands was reduced in the thymus and peripheral lymphoid tissues, suggesting a potential role of TNFR2 in promoting the sustained expression of FoxP3. We observed that upon in vitro activation with plate-bound antiCD3 Ab and soluble anti-CD28 Ab, FoxP3 expression by highly purified mouse Tregs was markedly down-regulated. Importantly, TNF partially abrogated this effect of TCR stimulation and stabilized FoxP3 expression. This effect of TNF was blocked by anti-TNFR2 Ab, but not by anti-TNFR1 Ab. Furthermore, TNF was not able to maintain FoxP3 expression by TNFR2- deficient Tregs. In mouse colitis model induced by transfer of naïve CD4 cells into Rag1−/− mice, the disease could be inhibited by co-transfer of WT Tregs, but not by co-transfer of TNFR2- deficient Tregs. Furthermore, in the lamina propria of the colitis model, the majority of WT Tregs maintained FoxP3 expression. In contrast, increased number of TNFR2-deficient Tregs lost FoxP3 expression. Thus, our data clearly show that TNFR2 is critical for the phenotypic and functional stability of Treg in the inflammatory environment. This effect of TNF should be taken into account when designing future therapy of autoimmunity and GVHD by using TNF inhibitors.

DOIhttp://doi.org/10.4049/jimmunol.1202659
Indexed BySCI
Language英语
WOS Research AreaImmunology
WOS SubjectImmunology
WOS IDWOS:000313784200026
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Cited Times [WOS]:128   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorXin Chen
Affiliation1.Basic Science Program, SAIC-Frederick, Inc.; NCI-Frederick
2.Laboratory of Molecular Immunoregulation; Center for Cancer Research, NCI-Frederick, Frederick, Maryland 21702-1201
3.Department of Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
Recommended Citation
GB/T 7714
Xin Chen,Xueqing Wu,Qiong Zhou,et al. TNFR2 Is Critical for the Stabilization of the CD4+ Foxp3+ Regulatory T Cell Phenotype in the Inflammatory Environment[J]. JOURNAL OF IMMUNOLOGY,2013,190(3):1076-1084.
APA Xin Chen,Xueqing Wu,Qiong Zhou,O.M. Zack Howard,Mihai G. Netea,&Joost J. Oppenheim.(2013).TNFR2 Is Critical for the Stabilization of the CD4+ Foxp3+ Regulatory T Cell Phenotype in the Inflammatory Environment.JOURNAL OF IMMUNOLOGY,190(3),1076-1084.
MLA Xin Chen,et al."TNFR2 Is Critical for the Stabilization of the CD4+ Foxp3+ Regulatory T Cell Phenotype in the Inflammatory Environment".JOURNAL OF IMMUNOLOGY 190.3(2013):1076-1084.
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