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micro RNA cluster 106a~363 is involved in T helper 17 cell differentiation
Author(s) -
Kästle Marc,
Bartel Sabine,
GeillingerKästle Kerstin,
Irmler Martin,
Beckers Johannes,
Ryffel Bernhard,
Eickelberg Oliver,
KraussEtschmann Susanne
Publication year - 2017
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12775
Subject(s) - rar related orphan receptor gamma , t helper cell , cellular differentiation , biology , interleukin 23 , nfat , transcription factor , microrna , microbiology and biotechnology , orphan receptor , rna , immunology , t cell , interleukin 17 , inflammation , foxp3 , immune system , genetics , gene
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 micro RNA s (mi RNA s) are critical regulators of signalling pathways, we aimed to identify specific mi RNA s 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 mi RNA 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 Cd 4 + 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 mi RNA s are involved in controlling the differentiation and function of T helper cells, offering useful tools to study and modify Th17‐mediated inflammation.