Nuclear Factor-kappa B Modulates Regulatory T Cell Development by Directly Regulating Expression of Foxp3 Transcription Factor

作者：Long Meixiao; Park Sung Gyoo; Strickland Ian; Hayden Mafthew S; Ghosh Sankar^*

来源：Immunity, 2009, 31(6): 921-931.

DOI：10.1016/j.immuni.2009.09.022

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)-kappa B activity via a constitutive active inhibitor of kappa B kinase beta (IKK beta) 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-kappa B pathway also induced Foxp3 expression in otherwise conventionally selected T cells. NF-kappa B directly promoted the transcription of Foxp3, and upon T cell receptor (TCR) stimulation, c-Rel, a NF-kappa B family member, bound to Foxp3 enhancer region, which is specifically demethylated in natural Treg cells. Hence, NF-kappa B signaling pathway is a key regulator of Foxp3 expression during natural Treg cell development.

• 出版日期2009-12-18