MicroRNA cluster 106a~363 is involved in T helper 17 cell differentiation. Issue 3 (28th July 2017)

• Record Type: Journal Article
• Authors: Kästle, Marc; Bartel, Sabine; Geillinger‐Kästle, Kerstin; Irmler, Martin; Beckers, Johannes; Ryffel, Bernhard; Eickelberg, Oliver; Krauss‐Etschmann, Susanne
• Is Part Of: Immunology. Volume 152:Issue 3(2017)
• Page Start: 402
• Page End: 413
• Publication Date: 2017-07-28
• Subjects: microRNA -- miR‐106a -- miR‐18b -- miR‐363a‐3p -- nuclear factor of activated T cells 5 -- retinoid‐related orphan receptor α -- retinoid‐related orphan receptor γt -- T helper cell differentiation -- T helper type 17; Immunology -- Periodicals
• DOI: 10.1111/imm.12775
• Languages: English
• ISSNs: 0019-2805

Abstract

Summary: T‐helper cell type 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 T helper subtypes needs to be tightly regulated to ensure an immunological balance. As microRNAs (miRNAs) are critical regulators of signalling pathways, we aimed to identify specific miRNAs implicated in controlling Th17 differentiation. We were able to create a regulatory network model of murine T helper 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, whereas 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‐106a and miR‐363‐3p into primary murine Cd4 + lymphocytes decreased expression of retinoid‐related orphan receptor c ( Rorc ), Rora, Il17a and Il17f, and abolished secretion of Th17‐mediated interleukin‐17a (Il17a). 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. Abstract : By combining mRNA and miRNA microarray analysis of in vitro differentiated T helper type 2 (Th2) and Th17 cells, we generated an in silico regulatory network model or Th cell differentiation. Further, we identified miR‐18b, miR‐106a and miR‐363‐3p to specifically target Th17 transcription factors Rora, Nfat5 and Rorc and thus to be involved in Th17 differentiation and function. 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.