[PDF][PDF] Nuclear factor-κB modulates regulatory T cell development by directly regulating expression of Foxp3 transcription factor

M Long, SG Park, I Strickland, MS Hayden, S Ghosh - Immunity, 2009 - cell.com
M Long, SG Park, I Strickland, MS Hayden, S Ghosh
Immunity, 2009cell.com
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)-κB activity via a constitutive active
inhibitor of κB kinase β (IKKβ) 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-κB pathway also induced …
Summary
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)-κB activity via a constitutive active inhibitor of κB kinase β (IKKβ) 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-κB pathway also induced Foxp3 expression in otherwise conventionally selected T cells. NF-κB directly promoted the transcription of Foxp3, and upon T cell receptor (TCR) stimulation, c-Rel, a NF-κB family member, bound to Foxp3 enhancer region, which is specifically demethylated in natural Treg cells. Hence, NF-κB signaling pathway is a key regulator of Foxp3 expression during natural Treg cell development.
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