Selective miRNA disruption in T reg cells leads to uncontrolled autoimmunity

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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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)
UniBasel Contributors:Jeker, Lukas T.
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Rockefeller University Press
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:16 Dec 2020 10:45
Deposited On:16 Dec 2020 10:45

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