期刊
IMMUNITY
卷 31, 期 6, 页码 921-931出版社
CELL PRESS
DOI: 10.1016/j.immuni.2009.09.022
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类别
资金
- NIH [R37 AI33443, R01 AI068977, T32AI007019-33]
- NIH/NIGMS MSTP [GM07205]
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.
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