Zhou, Xuyu and Jeker, Lukas T. and Fife, Brian T. and Zhu, Shirley and Anderson, Mark S. and McManus, Michael T. and Bluestone, Jeffrey A.. (2008) Selective miRNA disruption in T reg cells leads to uncontrolled autoimmunity. Journal of Experimental Medicine, 205 (9). pp. 1983-1991.
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Official URL: https://edoc.unibas.ch/61964/
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Abstract
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.
Faculties and Departments: | 03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Molecular Immune Regulation (Jeker) |
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UniBasel Contributors: | Jeker, Lukas T. |
Item Type: | Article, refereed |
Article Subtype: | Research Article |
Publisher: | Rockefeller University Press |
ISSN: | 0022-1007 |
e-ISSN: | 1540-9538 |
Note: | Publication type according to Uni Basel Research Database: Journal article |
Related URLs: | |
Identification Number: |
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Last Modified: | 16 Dec 2020 10:45 |
Deposited On: | 16 Dec 2020 10:45 |
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