MicroRNA-21 promotes Th17 differentiation and mediates experimental autoimmune encephalomyelitis

Accumulation of IL-17-producing Th17 cells is associated with the development of multiple autoimmune diseases; however, the contribution of microRNA (miRNA) pathways to the intrinsic control of Th17 development remains unclear. Here, we demonstrated that miR-21 expression is elevated in Th17 cells a...

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Vydáno v:The Journal of clinical investigation Ročník 125; číslo 3; s. 1069 - 1080
Hlavní autoři: Murugaiyan, Gopal, da Cunha, Andre Pires, Ajay, Amrendra K., Joller, Nicole, Garo, Lucien P., Kumaradevan, Sowmiya, Yosef, Nir, Vaidya, Vishal S., Weiner, Howard L.
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States American Society for Clinical Investigation 01.03.2015
Témata:
Animals
Autoimmune diseases
Base Sequence
Binding Sites
Biomedical research
Care and treatment
Cell Differentiation
Cells, Cultured
Encephalomyelitis
Encephalomyelitis, Autoimmune, Experimental - metabolism
Encephalomyelitis, Autoimmune, Experimental - pathology
Female
Gene Expression
Hospitals
Immune system
Interleukin-17 - genetics
Interleukin-17 - metabolism
Lymphocytes
Mice, Inbred C57BL
MicroRNA
MicroRNAs - physiology
Physiological aspects
Rheumatology
RNA Interference
Smad7 Protein - genetics
Smad7 Protein - metabolism
Studies
Th17 Cells - physiology
Transcription factors
ISSN:0021-9738, 1558-8238, 1558-8238
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Shrnutí:Accumulation of IL-17-producing Th17 cells is associated with the development of multiple autoimmune diseases; however, the contribution of microRNA (miRNA) pathways to the intrinsic control of Th17 development remains unclear. Here, we demonstrated that miR-21 expression is elevated in Th17 cells and that mice lacking miR-21 have a defect in Th17 differentiation and are resistant to experimental autoimmune encephalomyelitis (EAE). Furthermore, we determined that miR-21 promotes Th17 differentiation by targeting and depleting SMAD-7, a negative regulator of TGF-β signaling. Moreover, the decreases in Th17 differentiation in miR-21-deficient T cells were associated with defects in SMAD-2/3 activation and IL-2 suppression. Finally, we found that treatment of WT mice with an anti-miR-21 oligonucleotide reduced the clinical severity of EAE, which was associated with a decrease in Th17 cells. Thus, we have characterized a T cell-intrinsic miRNA pathway that enhances TGF-β signaling, limits the autocrine inhibitory effects of IL-2, and thereby promotes Th17 differentiation and autoimmunity.
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ISSN:0021-9738
1558-8238
1558-8238
DOI:10.1172/JCI74347