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Updated: Jun 17, 2026

In Vitro Differentiation of Human CD4+FOXP3+ Induced Regulatory T Cells (iTregs) from Naïve CD4+ T Cells Using a TGF-β-containing Protocol
Published on: December 30, 2016
Nuclear factor-kappaB modulates regulatory T cell development by directly regulating expression of Foxp3
Meixiao Long1, Sung-Gyoo Park, Ian Strickland
1Department of Immunobiology and Molecular Biophysics & Biochemistry, Yale University School of Medicine, New Haven, CT 06520, USA.
Abstract:
Naturally derived regulatory T (Treg) cells are characterized by stable expression of the transcription factor Foxp3 and characteristic epigenetic imprinting at the Foxp3 gene locus. Here, we found that enhancing nuclear factor (NF)-kappaB activity via a constitutive active inhibitor of kappaB kinase beta (IKKbeta) transgene in T cells led to increased number of Foxp3(+) cells in the thymus and can rescue Foxp3 expression in thymocytes deficient in other pleiotropic signaling molecules. Enhancing the signal strength of the NF-kappaB pathway also induced Foxp3 expression in otherwise conventionally selected T cells. NF-kappaB directly promoted the transcription of Foxp3, and upon T cell receptor (TCR) stimulation, c-Rel, a NF-kappaB family member, bound to Foxp3 enhancer region, which is specifically demethylated in natural Treg cells. Hence, NF-kappaB signaling pathway is a key regulator of Foxp3 expression during natural Treg cell development.
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