MicroRNA-21 promotes Th17 differentiation and mediates experimental autoimmune encephalomyelitis

Gopal Murugaiyan, Andre Pires da Cunha, Amrendra K. Ajay, Nicole Joller, Lucien P. Garo, Sowmiya Kumaradevan, Nir Yosef, Vishal S. Vaidya, Howard L. Weiner

Research output: Contribution to journalArticlepeer-review


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-beta 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-beta signaling, limits the autocrine inhibitory effects of IL-2, and thereby promotes Th17 differentiation and autoimmunity.
Original languageEnglish
Pages (from-to)1069-1080
Number of pages12
JournalThe Journal of Clinical Investigation
Issue number3
Early online date2 Feb 2015
StatePublished - 1 Mar 2015


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