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.
Gopal Murugaiyan, Andre Pires da Cunha, Amrendra K. Ajay, Nicole Joller, Lucien P. Garo, Sowmiya Kumaradevan, Nir Yosef, Vishal S. Vaidya, Howard L. Weiner
Usage data is cumulative from November 2023 through November 2024.
Usage | JCI | PMC |
---|---|---|
Text version | 1,222 | 152 |
168 | 32 | |
Figure | 305 | 44 |
Supplemental data | 48 | 4 |
Citation downloads | 53 | 0 |
Totals | 1,796 | 232 |
Total Views | 2,028 |
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.