title: MicroRNA-21 promotes Th17 differentiation and mediates experimental autoimmune encephalomyelitis.
abstract: 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.
authors: Gopal
authors: G
authors: Murugaiyan
authors: Andre Pires
authors: AP
authors: da Cunha
authors: Amrendra K
authors: AK
authors: Ajay
authors: Nicole
authors: N
authors: Joller
authors: Lucien P
authors: LP
authors: Garo
authors: Sowmiya
authors: S
authors: Kumaradevan
authors: Nir
authors: N
authors: Yosef
authors: Vishal S
authors: VS
authors: Vaidya
authors: Howard L
authors: HL
authors: Weiner
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002454:Cell Differentiation; D002478:Cells, Cultured; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000502:physiology*; D034622:RNA Interference; D051906:Smad7 Protein / Q000235:genetics / Q000378:metabolism; D058504:Th17 Cells / Q000502:physiology*
chemical_list: D020381:Interleukin-17; C531950:MIRN21 microRNA, mouse; D035683:MicroRNAs; D051906:Smad7 Protein; C497807:Smad7 protein, mouse
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