| First Author | Lim YJ | Year | 2024 |
| Journal | Cell Rep | Volume | 43 |
| Issue | 8 | Pages | 114565 |
| PubMed ID | 39083380 | Mgi Jnum | J:353918 |
| Mgi Id | MGI:7716350 | Doi | 10.1016/j.celrep.2024.114565 |
| Citation | Lim YJ, et al. (2024) MicroRNA-19b exacerbates systemic sclerosis through promoting Th9 cells. Cell Rep 43(8):114565 |
| abstractText | Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by fibrosis of the skin and multiple vital organs, but the immunological pathogenesis of SSc remains unclear. We show here that miR-19b promotes Th9 cells that exacerbate SSc. Specifically, miR-19b and interleukin (IL)-9 increase in CD4(+) T cells in experimental SSc in mice induced with bleomycin. Inhibiting miR-19b reduces Th9 cells and ameliorates the disease. Mechanistically, transforming growth factor beta (TGF-beta) plus IL-4 activates pSmad3-Ser(213) and TRAF6-K63 ubiquitination by suppressing NLRC3. Activated TRAF6 sequentially promotes TGF-beta-activated kinase 1 (TAK1) and nuclear factor kappaB (NF-kappaB) p65 phosphorylation, leading to the upregulation of miR-19b. Notably, miR-19b activated Il9 gene expression by directly suppressing atypical E2F family member E2f8. In patients with SSc, higher levels of IL9 and MIR-19B correlate with worse disease progression. Our findings reveal miR-19b as a key factor in Th9 cell-mediated SSc pathogenesis and should have clinical implications for patients with SSc. |
