Ubiquitin Activating Enzyme UBA6 Regulates Th1 and Tc1 Cell Differentiation.
Cells
; 11(1)2021 12 29.
Article
em En
| MEDLINE
| ID: mdl-35011668
ABSTRACT
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-γ). 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-γ 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 IκBα degradation, thereby increasing NF-κB p65 activation in the T cells. Our study identifies UBA6 as a critical regulator of IFN-γ production in T cells by modulating the NF-κB p65 activation pathway.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T Citotóxicos
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Diferenciação Celular
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Células Th1
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Enzimas Ativadoras de Ubiquitina
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Revista:
Cells
Ano de publicação:
2021
Tipo de documento:
Article