Canonical microRNAs in thymic epithelial cells promote central tolerance

Khan, Imran S. and Taniguchi, Ruth T. and Fasano, Kayla J. and Anderson, Mark S. and Jeker, Lukas T.. (2014) Canonical microRNAs in thymic epithelial cells promote central tolerance. European Journal of Immunology, 44 (5). pp. 1313-1319.

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Official URL: https://edoc.unibas.ch/61957/

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Medullary thymic epithelial cells (mTECs) facilitate the deletion of developing self-reactive T cells by displaying a diverse repertoire of tissue-specific antigens, a process which largely depends on the expression of the autoimmune regulator (Aire) gene. Mature microRNAs (miRNAs) that regulate gene expression post-transcriptionally are generated in a multistep process. The microprocessor complex, including DGCR8, cleaves canonical miRNAs, but alternative DGCR8-independent miRNA biogenesis pathways exist as well. In order to study the role of canonical miRNAs in thymic epithelial cells (TECs), we ablated Dgcr8 using a FoxN1-Cre transgene. We report that DGCR8-deficient TECs are unable to maintain proper thymic architecture and exhibit a dramatic loss of thymic cellularity. Importantly, DGCR8-deficient TECs develop a severe loss of Aire(+) mTECs. Using a novel immunization approach to amplify and detect self-reactive T cells within a polyclonal TCR repertoire, we demonstrate a link between the loss of Aire expression in DGCR8-deficient TECs and the breakdown of negative selection in the thymus. Thus, DGCR8 and canonical miRNAs are important in TECs for supporting central tolerance.
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
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:16 Dec 2020 07:49
Deposited On:16 Dec 2020 07:49

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