Targeted delivery of Fc-fused PD-L1 for effective management of acute and chronic colitis.
Nat Commun
; 15(1): 1673, 2024 Feb 23.
Article
en En
| MEDLINE
| ID: mdl-38396052
ABSTRACT
The PD-1/PD-L1 pathway in mucosal immunity is currently actively explored and considered as a target for inflammatory bowel disease (IBD) treatment. However, systemic PD-L1 administration may cause unpredictable adverse effects due to immunosuppression. Here we show that reactive oxygen species (ROS)-responsive nanoparticles enhance the efficacy and safety of PD-L1 in a mouse colitis model. The nanoparticles control the accumulation and release of PD-L1 fused to Fc (PD-L1-Fc) at inflammatory sites in the colon. The nanotherapeutics shows superiority in alleviating inflammatory symptoms over systemic PD-L1-Fc administration and mitigates the adverse effects of PD-L1-Fc administration. The nanoparticles-formulated PD-L1-Fc affects production of proinflammatory and anti-inflammatory cytokines, attenuates the infiltration of macrophages, neutrophils, and dendritic cells, increases the frequencies of Treg, Th1 and Tfh cells, reshapes the gut microbiota composition; and increases short-chain fatty acid production. In summary, PD-L1-Fc-decorated nanoparticles may provide an effective and safe strategy for the targeted treatment of IBD.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Enfermedades Inflamatorias del Intestino
/
Colitis
Límite:
Animals
Idioma:
En
Revista:
Nat Commun
Asunto de la revista:
BIOLOGIA
/
CIENCIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Reino Unido