| First Author | Zhou X | Year | 2008 |
| Journal | J Exp Med | Volume | 205 |
| Issue | 9 | Pages | 1983-91 |
| PubMed ID | 18725525 | Mgi Jnum | J:138808 |
| Mgi Id | MGI:3806417 | Doi | 10.1084/jem.20080707 |
| Citation | Zhou X, et al. (2008) Selective miRNA disruption in T reg cells leads to uncontrolled autoimmunity. J Exp Med 205(9):1983-91 |
| abstractText | A new regulatory T (T reg) cell-specific, FoxP3-GFP-hCre bacterial artificial chromosome transgenic mouse was crossed to a conditional Dicer knockout (KO) mouse strain to analyze the role of microRNAs (miRNAs) in the development and function of T reg cells. Although thymic T reg cells developed normally in this setting, the cells showed evidence of altered differentiation and dysfunction in the periphery. Dicer-deficient T reg lineage cells failed to remain stable, as a subset of cells down-regulated the T reg cell-specific transcription factor FoxP3, whereas the majority expressed altered levels of multiple genes and proteins (including Neuropilin 1, glucocorticoid-induced tumor necrosis factor receptor, and cytotoxic T lymphocyte antigen 4) associated with the T reg cell fingerprint. In fact, a significant percentage of the T reg lineage cells took on a T helper cell memory phenotype including increased levels of CD127, interleukin 4, and interferon gamma. Importantly, Dicer-deficient T reg cells lost suppression activity in vivo; the mice rapidly developed fatal systemic autoimmune disease resembling the FoxP3 KO phenotype. These results support a central role for miRNAs in maintaining the stability of differentiated T reg cell function in vivo and homeostasis of the adaptive immune system. |
