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• W2036782104 startingPage "e20003" @default.
• W2036782104 abstract "Naturally occurring CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cells develop in the thymus and represent a mature T cell subpopulation critically involved in maintaining peripheral tolerance. The differentiation of Treg cells in the thymus requires T cell receptor (TCR)/CD28 stimulation along with cytokine-promoted Foxp3 induction. TCR-mediated nuclear factor kappa B (NF-κB) activation seems to be involved in differentiation of Treg cells because deletion of components of the NF-κB signaling pathway, as well as of NF-κB transcription factors, leads to markedly decreased Treg cell numbers in thymus and periphery.To investigate if Treg cell-intrinsic NF-κB activation is required for thymic development and peripheral homeostasis of Treg cells we used transgenic (Tg) mice with thymocyte-specific expression of a stable IκBα mutant to inhibit NF-κB activation solely within the T cell lineage. Here we show that Treg cell-intrinsic NF-κB activation is important for the generation of cytokine-responsive Foxp3(-) thymic Treg precursors and their further differentiation into mature Treg cells. Treg cell development could neither be completely rescued by the addition of exogenous Interleukin 2 (IL-2) nor by the presence of wild-type derived cells in adoptive transfer experiments. However, peripheral NF-κB activation appears to be required for IL-2 production by conventional T cells, thereby participating in Treg cell homeostasis. Moreover, pharmacological NF-κB inhibition via the IκB kinase β (IKKβ) inhibitor AS602868 led to markedly diminished thymic and peripheral Treg cell frequencies.Our results indicate that Treg cell-intrinsic NF-κB activation is essential for thymic Treg cell differentiation, and further suggest pharmacological NF-κB inhibition as a potential therapeutic approach for manipulating this process." @default.
• W2036782104 created "2016-06-24" @default.
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• W2036782104 date "2011-05-18" @default.
• W2036782104 modified "2023-10-17" @default.
• W2036782104 title "Cell-Intrinsic NF-κB Activation Is Critical for the Development of Natural Regulatory T Cells in Mice" @default.
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• W2036782104 doi "https://doi.org/10.1371/journal.pone.0020003" @default.
• W2036782104 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3097234" @default.
• W2036782104 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/21625598" @default.
• W2036782104 hasPublicationYear "2011" @default.
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