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TNF-alpha: An Activator of CD4+FoxP3+TNFR2+ Regulatory T Cells
Chen, X.; Oppenheim, J.
2010-02-18
Source PublicationTNF Pathophysiology. Molecular and Cellular Mechanisms. Curr Dir Autoimmun.
Publication PlaceBasel
PublisherKarger, Postfach, CH-4009 Basel (Switzerland)
Pages119-134
AbstractTNF-alpha (TNF) is a pleiotropic cytokine which can have proinflammatory or immunosuppressive effects, depending on the context, duration of exposure and disease state. The basis for the opposing actions of TNF remains elusive. The growing appreciation of CD4+FoxP3+ regulatory T cells (Tregs), which comprise similar to 10% of peripheral CD4 cells, as pivotal regulators of immune responses has provided a new framework to define the cellular and molecular basis underlying the contrasting action of TNF. TNF by itself can overcome the profound anergic state of T cell receptor-stimulated Tregs. Furthermore, in concert with IL-2, TNF selectively activates Tregs, resulting in proliferation, upregulation of FoxP3 expression and increases in their suppressive activity. Both human and mouse Tregs predominantly express TNFR2, making it possible for TNF to enhance Treg activity, which helps limit the collateral damage caused by excessive immune responses and eventually terminates immune response. TNFR2-expressing CD4+FoxP3+ Tregs comprise similar to 40% of peripheral Tregs in normal mice and present the maximally suppressive subset of Tregs. In this review, studies describing the action of TNF on Treg function will be discussed. The role of Tregs in the autoimmune disorders and cancer as well as the effect of anti-TNF therapy on Tregs, especially in rheumatoid arthritis, will also be considered.
KeywordTNF RHEUMATOID ARTHRITIS PERTUSSIS TOXIN
URLView the original
Language英語English
ISBN9783805593830
The Source to ArticlePB_Publication
PUB ID34766
Document TypeBook chapter
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorChen, X.
Recommended Citation
GB/T 7714
Chen, X.,Oppenheim, J.. TNF-alpha: An Activator of CD4+FoxP3+TNFR2+ Regulatory T Cells[M]. TNF Pathophysiology. Molecular and Cellular Mechanisms. Curr Dir Autoimmun., Basel:Karger, Postfach, CH-4009 Basel (Switzerland), 2010, 119-134.
APA Chen, X.., & Oppenheim, J. (2010). TNF-alpha: An Activator of CD4+FoxP3+TNFR2+ Regulatory T Cells. TNF Pathophysiology. Molecular and Cellular Mechanisms. Curr Dir Autoimmun., 119-134.
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