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Interaction of TNF and TNFR2 stabilizes the phenotype and function of CD4+FoxP3+regulatory T cells in the inflammatory environment
Chen, X1; Wu, XQ2; Howard, OMZ2; Oppenheim, J2
2012
Conference Name99th Annual Meeting of the American-Association-of-Immunologists
Source PublicationJOURNAL OF IMMUNOLOGY
Volume188
Issue1
Conference DateMAY 04-08, 2012
Conference PlaceBoston, MA
Abstract

Our previous results showed that TNF-TNFR2 signaling promotes activation and expansion of Tregs. Thus we hypothesize that TNF-TNFR2 signaling may play a critical role in maintaining phenotypic and functional stability of Tregs during an inflammatory response. We were able to confirm that, in colitis model induced by transfer of naïve CD4 cells into Rag KO mice, the disease could be inhibited by co-transfer of WT Tregs, but not by co-transfer of TNFR2-deficient Tregs. Furthermore, in the colon 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. In vitro, FoxP3 expression by highly purified Tregs was reduced to almost undetectable levels after potent TCR-stimulation, which was partially abrogated by TNF. This effect of TNF was blocked by anti-TNFR2 Ab, but not by anti-TNFR1 Ab. In addition, TNF was not able to increase FoxP3 expression by TNFR2-deficient Tregs undergoing TCR-stimulation. A full mouse genome array study revealed that, as compared with TNFR2- Tregs, TNFR2+ Tregs from normal mice expressed 4-fold lower levels of a gene encoding SATB1, in line with a recent study show that the repression of this genome organizer play a crucial role in maintenance of Treg phenotype and function. Thus, our data clearly show that the TNF-TNFR2 signaling is critical for the phenotypic and functional stability of Treg in the inflammatory environment.

Indexed BySCI
Language英语
WOS Research AreaImmunology
WOS SubjectImmunology
WOS IDWOS:000304659702285
Fulltext Access
Citation statistics
Document TypeConference paper
CollectionInstitute of Chinese Medical Sciences
Affiliation1.NCI, Basic Sci Program, SAIC Frederick Inc, Frederick, MD 21701 USA
2.NCI, LMI CIP CCR, Frederick, MD 21701 USA
Recommended Citation
GB/T 7714
Chen, X,Wu, XQ,Howard, OMZ,et al. Interaction of TNF and TNFR2 stabilizes the phenotype and function of CD4+FoxP3+regulatory T cells in the inflammatory environment[C],2012.
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