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Kaestle, M. ; Bartel, S. ; Geillinger-Kästle, K.* ; Irmler, M. ; Beckers, J. ; Ryffel, B.* ; Eickelberg, O. ; Krauss-Etschmann, S.

microRNA cluster 106a~363 is involved in T-Helper 17 (Th17) cell differentiation.

Immunology 152, 402-413 (2017)
Publ. Version/Full Text Postprint DOI PMC
Open Access Green
T-helper cell 17 (Th17) mediated inflammation is associated with various diseases including autoimmune encephalitis, inflammatory bowel disease and lung diseases such as chronic obstructive pulmonary disease and asthma. Differentiation into distinct Th subtypes needs to be tightly regulated to ensure an immunological balance. As microRNAs (miRNAs) are critical regulators of signaling pathways, we aimed to identify specific miRNAs implicated in controlling Th17 differentiation. We were able to create a regulatory network model of murine Th cell differentiation by combining Affymetrix mRNA and miRNA arrays and in-silico analysis. In this model, the miR-212~132 and miR-182~183 clusters were significantly up-regulated upon Th17 differentiation, while the entire miR-106~363 cluster was down regulated and predicted to target well-known Th17 cell differentiation pathways. In-vitro transfection of miR-18b, miR-106 and miR-363 into primary murine CD4(+) lymphocytes decreased expression of retinoid-related orphan receptor c (Rorc), Rora, Il17a and Il17f, and abolished secretion of Th17 mediated Il17-a. Moreover, we demonstrated target site-specific regulation of the Th17 transcription factors Rora and nuclear factor of activated T-cells (Nfat) 5 by miR-18b, miR-106a and miR-363-3p through luciferase reporter assays. Here, we provide evidence that miRNAs are involved in controlling the differentiation and function of T-helper cells, offering useful tools to study and modify Th17 mediated inflammation.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Ror α ; Nfat5 ; Rorγt ; T Helper Cell Differentiation ; Th17 ; Mir-106a ; Mir-18b ; Mir-363a-3p ; Microrna; Autoimmune Inflammation; Transcription Factor; Ror-gamma; Expression; Responses; Il-23; Metastasis; Induction; Mir-182; Mir-20b
ISSN (print) / ISBN 0019-2805
e-ISSN 1365-2567
Journal Immunology
Quellenangaben Volume: 152, Issue: 3, Pages: 402-413 Article Number: , Supplement: ,
Publisher Wiley
Publishing Place Hoboken
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Lung Health and Immunity (LHI)
Institute of Experimental Genetics (IEG)
Institute of Lung Biology (LHI)