Pathological role of activated mTOR in CXCR3+ memory B cells of rheumatoid arthritis.
Rheumatology (Oxford)
; 60(11): 5452-5462, 2021 11 03.
Article
en En
| MEDLINE
| ID: mdl-33693564
ABSTRACT
OBJECTIVES:
B cells play an important pathological role in RA. In this study, we investigated the role of metabolic regulator mTOR in B cells and its relevance to the pathology of RA.METHODS:
Peripheral blood mononuclear cells were isolated from 31 normal subjects and 86 RA patients and the gated B cells were assessed for mTOR phosphorylation and chemokine receptor expression. In vitro studies on peripheral blood B cells isolated from the control and RA patients investigated the molecular mechanisms.RESULTS:
Higher concentrations of CXCL10 (CXCR3 ligands) and lower percentages of CXCR3+ memory B cells were present in the peripheral blood of RA patients relative to the control. RA patients with high CXCL10 concentrations had smaller percentage of CXCR3+ memory B cells and high disease activity. One-year treatment with TNF inhibitors increased the percentage of CXCR3+ memory B cells and reduced serum CXCL10 concentrations. mTOR phosphorylation in B cells was further enhanced in RA patients, compared with the control, and was selectively enhanced in CXCR3+ memory B cells. mTOR phosphorylation in CXCR3+ memory B cells correlated with disease activity. In vitro, mTOR phosphorylation in B cells enhanced IL-6 production and increased RANKL expression.CONCLUSION:
mTOR activation in CXCR3+ memory B cells of RA patients is associated with disease activity, mediated through IL-6 production and RANKL expression. The obtained results also suggest that TNF inhibitors mediate an impact on the association between CXCL10 and mTOR activated CXCR3+ memory B cells.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Artritis Reumatoide
/
Linfocitos B
/
Serina-Treonina Quinasas TOR
Tipo de estudio:
Observational_studies
/
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Rheumatology (Oxford)
Asunto de la revista:
REUMATOLOGIA
Año:
2021
Tipo del documento:
Article
País de afiliación:
Japón