Metabolic preconditioning in CD4+ T cells restores inducible immune tolerance in lupus-prone mice.
JCI Insight
; 6(19)2021 10 08.
Article
en En
| MEDLINE
| ID: mdl-34403367
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Linfocitos T CD4-Positivos
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Antígenos Comunes de Leucocito
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Desoxiglucosa
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Hipoglucemiantes
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Tolerancia Inmunológica
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Riñón
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Lupus Eritematoso Sistémico
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Metformina
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Antimetabolitos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
JCI Insight
Año:
2021
Tipo del documento:
Article
Pais de publicación:
Estados Unidos