| First Author | Long M | Year | 2009 |
| Journal | Immunity | Volume | 31 |
| Issue | 6 | Pages | 921-31 |
| PubMed ID | 20064449 | Mgi Jnum | J:156178 |
| Mgi Id | MGI:4419026 | Doi | 10.1016/j.immuni.2009.09.022 |
| Citation | Long M, et al. (2009) Nuclear factor-kappaB modulates regulatory T cell development by directly regulating expression of Foxp3 transcription factor. Immunity 31(6):921-31 |
| abstractText | 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. |
