| First Author | Barbarulo A | Year | 2011 |
| Journal | J Immunol | Volume | 186 |
| Issue | 11 | Pages | 6199-206 |
| PubMed ID | 21508258 | Mgi Jnum | J:173214 |
| Mgi Id | MGI:5013546 | Doi | 10.4049/jimmunol.1002136 |
| Citation | Barbarulo A, et al. (2011) Notch3 and Canonical NF-{kappa}B Signaling Pathways Cooperatively Regulate Foxp3 Transcription. J Immunol 186(11):6199-206 |
| abstractText | Notch3 overexpression has been previously shown to positively regulate the generation and function of naturally occurring regulatory T cells and the expression of Foxp3, in cooperation with the pTalpha/pre-TCR pathway. In this study, we show that Notch3 triggers the trans activation of Foxp3 promoter depending on the T cell developmental stage. Moreover, we discovered a novel CSL/NF-kappaB overlapping binding site within the Foxp3 promoter, and we demonstrate that the activation of NF-kappaB, mainly represented by p65-dependent canonical pathway, plays a positive role in Notch3-dependent regulation of Foxp3 transcription. Accordingly, the deletion of protein kinase C, which mediates canonical NF-kappaB activation, markedly reduces regulatory T cell number and per cell Foxp3 expression in transgenic mice with a constitutive activation of Notch3 signaling. Collectively, our data indicate that the cooperation among Notch3, protein kinase C, and p65/NF-kappaB subunit modulates Foxp3 expression, adding new insights in the understanding of the molecular mechanisms involved in regulatory T cell homeostasis and function. |
