NAMPT is a metabolic checkpoint of IFNγ-producing CD4+ T cells in lupus nephritis.
Mol Ther
; 31(1): 193-210, 2023 01 04.
Article
em En
| MEDLINE
| ID: mdl-36146932
ABSTRACT
Interferon γ (IFNγ) produced by T cells represents the featured cytokine and is central to the pathogenesis of lupus nephritis (LN). Here, we identified nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the salvage NAD+ biosynthetic pathway, as playing a key role in controlling IFNγ production by CD4+ T cells in LN. Our data revealed that CD4+ T cells from LN showed an enhanced NAMPT-mediated NAD+ biosynthetic process, which was positively correlated with IFNγ production in CD4+ T cells. NAMPT promoted aerobic glycolysis and mitochondrial respiration in CD4+ T cells from patients with LN or MRL/lpr mice through the production of NAD+. By orchestrating metabolic fitness, NAMPT promoted translational efficiency of Ifng in CD4+ T cells. In vivo, knockdown of NAMPT by small interfering RNA (siRNA) or pharmacological inhibition of NAMPT by FK866 suppressed IFNγ production in CD4+ T cells, leading to reduced inflammatory infiltrates and ameliorated kidney damage in lupus mice. Taken together, this study uncovers a metabolic checkpoint of IFNγ-producing CD4+ T cells in LN in which therapeutically targeting NAMPT has the potential to normalize metabolic competence and blunt pathogenicity of CD4+ T cells in LN.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Nefrite Lúpica
/
Interferon gama
Limite:
Animals
Idioma:
En
Revista:
Mol Ther
Assunto da revista:
BIOLOGIA MOLECULAR
/
TERAPEUTICA
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
China