Metabolic preconditioning in CD4+ T cells restores inducible immune tolerance in lupus-prone mice.
JCI Insight
; 6(19)2021 10 08.
Article
em En
| MEDLINE
| ID: mdl-34403367
ABSTRACT
Autoimmune disease has presented an insurmountable barrier to restoration of durable immune tolerance. Previous studies indicate that chronic therapy with metabolic inhibitors can reduce autoimmune inflammation, but it remains unknown whether acute metabolic modulation enables permanent immune tolerance to be established. In an animal model of lupus, we determined that targeting glucose metabolism with 2-deoxyglucose (2DG) and mitochondrial metabolism with metformin enables endogenous immune tolerance mechanisms to respond to tolerance induction. A 2-week course of 2DG and metformin, when combined with tolerance-inducing therapy anti-CD45RB, prevented renal deposition of autoantibodies for 6 months after initial treatment and restored tolerance induction to allografts in lupus-prone mice. The restoration of durable immune tolerance was linked to changes in T cell surface glycosylation patterns, illustrating a role for glycoregulation in immune tolerance. These findings indicate that metabolic therapy may be applied as a powerful preconditioning to reinvigorate tolerance mechanisms in autoimmune and transplant settings that resist current immune therapies.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T CD4-Positivos
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Antígenos Comuns de Leucócito
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Desoxiglucose
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Hipoglicemiantes
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Tolerância Imunológica
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Rim
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Lúpus Eritematoso Sistêmico
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Metformina
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Antimetabólitos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
JCI Insight
Ano de publicação:
2021
Tipo de documento:
Article