| First Author | Sekiya T | Year | 2015 |
| Journal | J Exp Med | Volume | 212 |
| Issue | 10 | Pages | 1623-40 |
| PubMed ID | 26304965 | Mgi Jnum | J:227557 |
| Mgi Id | MGI:5701561 | Doi | 10.1084/jem.20142088 |
| Citation | Sekiya T, et al. (2015) Suppression of Th2 and Tfh immune reactions by Nr4a receptors in mature T reg cells. J Exp Med 212(10):1623-40 |
| abstractText | Regulatory T (T reg) cells are central mediators of immune suppression. As such, T reg cells are characterized by a distinct pattern of gene expression, which includes up-regulation of immunosuppressive genes and silencing of inflammatory cytokine genes. Although an increasing number of transcription factors that regulate T reg cells have been identified, the mechanisms by which the T reg cell-specific transcriptional program is maintained and executed remain largely unknown. The Nr4a family of nuclear orphan receptors, which we recently identified as essential for the development of T reg cells, is highly expressed in mature T reg cells as well, suggesting that Nr4a factors play important roles even beyond T reg cell development. Here, we showed that deletion of Nr4a genes specifically in T reg cells caused fatal systemic immunopathology. Nr4a-deficient T reg cells exhibited global alteration of the expression of genes which specify the T reg cell lineage, including reduction of Foxp3 and Ikzf4. Furthermore, Nr4a deficiency abrogated T reg cell suppressive activities and accelerated conversion to cells with Th2 and follicular helper T (Tfh) effector-like characteristics, with heightened expression of Th2 and Tfh cytokine genes. These findings demonstrate that Nr4a factors play crucial roles in mature T reg cells by directly controlling a genetic program indispensable for T reg cell maintenance and function. |
