| First Author | Kurowska-Stolarska M | Year | 2017 |
| Journal | Nat Commun | Volume | 8 |
| Pages | 15877 | PubMed ID | 28639625 |
| Mgi Jnum | J:250394 | Mgi Id | MGI:5920845 |
| Doi | 10.1038/ncomms15877 | Citation | Kurowska-Stolarska M, et al. (2017) MicroRNA-34a dependent regulation of AXL controls the activation of dendritic cells in inflammatory arthritis. Nat Commun 8:15877 |
| abstractText | Current treatments for rheumatoid arthritis (RA) do not reverse underlying aberrant immune function. A genetic predisposition to RA, such as HLA-DR4 positivity, indicates that dendritic cells (DC) are of crucial importance to pathogenesis by activating auto-reactive lymphocytes. Here we show that microRNA-34a provides homoeostatic control of CD1c+ DC activation via regulation of tyrosine kinase receptor AXL, an important inhibitory DC auto-regulator. This pathway is aberrant in CD1c+ DCs from patients with RA, with upregulation of miR-34a and lower levels of AXL compared to DC from healthy donors. Production of pro-inflammatory cytokines is reduced by ex vivo gene-silencing of miR-34a. miR-34a-deficient mice are resistant to collagen-induced arthritis and interaction of DCs and T cells from these mice are reduced and do not support the development of Th17 cells in vivo. Our findings therefore show that miR-34a is an epigenetic regulator of DC function that may contribute to RA. |
