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Cited by 781

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

TNF downmodulates the function of human CD4+CD25hi T-regulatory cells

Open access
Valencia, Xavier, Stephens, Geoffrey, Goldbach-Mansky, Raphaela, Wilson, Mildred, Shevach, Ethan M., Lipsky, Peter E.·2006·Blood

Abstract

CD4+CD25+ T-regulatory cells (Tregs) play an essential role in maintaining immunologic homeostasis and preventing autoimmunity. However, little is known about the exogenous factors that regulate their differentiation and function. Here, we report that TNF inhibits the suppressive function of both naturally occurring CD4+CD25+ Tregs and TGFβ1-induced CD4+CD25+ T-regulatory cells. The mechanism of this inhibition involves signaling through TNFRII that is constitutively expressed selectively on unstimulated Tregs and that is up-regulated by TNF. TNF-mediated inhibition of suppressive function is related to a decrease in FoxP3 mRNA and protein expression by the Tregs. Notably, CD4+CD25hi Tregs isolated from patients with active rheumatoid arthritis (RA) expressed reduced levels of FoxP3 mRNA and protein and poorly suppressed the proliferation and cytokine secretion of CD4+ effector T cells in vitro. Treatment with anti-TNF antibody (infliximab) increased FOXP3 mRNA and protein expression by CD4+CD25hi Tregs and restored their suppressive function. Thus, TNF has a novel action in modulating autoimmunity, by inhibiting CD4+CD25+ Treg activity. (Blood. 2006;108:253-261)

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Metadata

Authors
Valencia, X., Stephens, G., Goldbach-Mansky, R., Wilson, M., Shevach, E. M., & Lipsky, P. E.
Venue
Blood
Published
2006-07-01
Volume
108
Issue
1
Pages
253-261
ISSN
  • 0006-4971 (ISSN-L)
  • 1528-0020
OpenAlex
W2123249923
Cited by
781
References
1
FWCI
20.43
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: TNF downmodulates the function of human CD4+CD25hi T-regulatory cells. https://app.cochat.ai/papers/10.1182/blood-2005-11-4567
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Valencia, X., Stephens, G., Goldbach-Mansky, R., Wilson, M., Shevach, E. M., & Lipsky, P. E. (2006). TNF downmodulates the function of human CD4+CD25hi T-regulatory cells. Blood. https://doi.org/10.1182/blood-2005-11-4567

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