| First Author | Lee JY | Year | 2021 |
| Journal | Cells | Volume | 11 |
| Issue | 1 | PubMed ID | 35011668 |
| Mgi Jnum | J:317409 | Mgi Id | MGI:6852880 |
| Doi | 10.3390/cells11010105 | Citation | Lee JY, et al. (2021) Ubiquitin Activating Enzyme UBA6 Regulates Th1 and Tc1 Cell Differentiation. Cells 11(1) |
| abstractText | Ubiquitination is a crucial mechanism in regulating the immune response, setting the balance between immunity and tolerance. Here, we investigated the function of a poorly understood alternative branch of the ubiquitin-activating E1 enzyme UBA6 in activating immune cells. UBA6 expression levels were elevated in T cells by toll-like receptor agonists and anti-CD3/28 antibody stimulation, but not in dendritic cells, macrophages, B cells, and natural killer cells. Additionally, we generated T cell-specific UBA6-deficient mice and found that UBA6-deficient CD4 and CD8 T cells elevated the production of interferon-gamma (IFN-gamma). Moreover, the transfer of UBA6-deficient CD4 and CD8 T cells in RAG1-knockout mice exacerbated the development of multi-organ inflammation compared with control CD4 and CD8 T cell transfer. In human peripheral blood CD4 and CD8 T cells, basal levels of UBA6 in lupus patients presented much lower than those in healthy controls. Moreover, the IFN-gamma production efficiency of CD4 and CD8 T cells was negatively correlated to UBA6 levels in patients with lupus. Finally, we found that the function of UBA6 was mediated by destabilization of IkappaBalpha degradation, thereby increasing NF-kappaB p65 activation in the T cells. Our study identifies UBA6 as a critical regulator of IFN-gamma production in T cells by modulating the NF-kappaB p65 activation pathway. |
