| First Author | Bettelli E | Year | 2005 |
| Journal | Proc Natl Acad Sci U S A | Volume | 102 |
| Issue | 14 | Pages | 5138-43 |
| PubMed ID | 15790681 | Mgi Jnum | J:97353 |
| Mgi Id | MGI:3575325 | Doi | 10.1073/pnas.0501675102 |
| Citation | Bettelli E, et al. (2005) Foxp3 interacts with nuclear factor of activated T cells and NF-{kappa}B to repress cytokine gene expression and effector functions of T helper cells. Proc Natl Acad Sci U S A 102(14):5138-43 |
| abstractText | Scurfy mice, which are deficient in a functional Foxp3, exhibit a severe lymphoproliferative disorder and display generalized over-production of cytokines. Here, we show that, among the Foxp transcriptional factor family, which includes Foxp1, Foxp2, and Foxp3, only Foxp3 has the ability to inhibit IL-2, IL-4, and IFN-gamma production by primary T helper cells. We found that Foxp3 physically associates with the Rel family transcription factors, nuclear factor of activated T cells (NFAT) and NF-kappaB, and blocks their ability to induce the endogenous expression of their target genes, including key cytokine genes. More importantly, T cells derived from scurfy mice have a dramatic increase in nuclear factor of activated T cells (NFAT) and NF-kappaB transcriptional activity compared with the T cells derived from WT mice. Furthermore, complementation of Foxp3 in scurfy-derived T cells lowers the NFAT and NF-kappaB transcriptional activity to the physiological level. Finally, we show that myelin proteolipid protein-specific autoreactive T cells transduced with Foxp3 cannot mediate experimental autoimmune encephalomyelitis, providing further support that Foxp3 suppresses the effector function of autoreactive T cells. Foxp3 has already been associated with the generation of CD4(+)CD25(+) regulatory T cells; our data additionally demonstrate that Foxp3 suppresses the effector functions of T helper cells by directly inhibiting the activity of two key transcription factors, NFAT and NF-kappaB, which are essential for cytokine gene expression and T cell functions. |
