| First Author | Beal AM | Year | 2011 |
| Journal | Nat Immunol | Volume | 13 |
| Issue | 1 | Pages | 77-85 |
| PubMed ID | 22080920 | Mgi Jnum | J:179003 |
| Mgi Id | MGI:5300858 | Doi | 10.1038/ni.2154 |
| Citation | Beal AM, et al. (2011) TGF-beta induces the expression of the adaptor Ndfip1 to silence IL-4 production during iT(reg) cell differentiation. Nat Immunol 13(1):77-85 |
| abstractText | Mice deficient in the adaptor Ndfip1 develop inflammation at sites of environmental antigen exposure. We show here that such mice had fewer inducible regulatory T cells (iT(reg) cells). In vitro, Ndfip1-deficient T cells expressed normal amounts of the transcription factor Foxp3 during the first 48 h of iT(reg) cell differentiation; however, this expression was not sustained. Abortive Foxp3 expression was caused by production of interleukin 4 (IL-4) by Ndfip1(-/-) cells. We found that Ndfip1 expression was transiently upregulated during iT(reg) cell differentiation in a manner dependent on transforming growth factor-beta (TGF-beta). Once expressed, Ndfip1 promoted degradation of the transcription factor JunB mediated by the E3 ubiquitin ligase Itch, thus preventing IL-4 production. On the basis of our data, we propose that TGF-beta signaling induces Ndfip1 expression to silence IL-4 production, thus permitting iT(reg) cell differentiation. |
