Immunosuppressive nanoparticles containing recombinant PD-L1 and methotrexate alleviate multi-organ inflammation.
Biomaterials
; 301: 122233, 2023 10.
Article
em En
| MEDLINE
| ID: mdl-37393694
ABSTRACT
Multi-organ inflammatory diseases are one of the most serious autoimmune diseases worldwide. The regulation of immune responses by immune checkpoint proteins influences the development and treatment of cancer and autoimmune diseases. In this study, recombinant murine PD-L1 (rmPD-L1) was used for controlling T cell immunity to treat multi-organ inflammation. To enhance the immunosuppressive effect, we incorporated methotrexate, an anti-inflammatory drug, into hybrid nanoparticles (HNPs) and decorated the surface of HNPs with rmPD-L1 to produce immunosuppressive HNPs (IsHNPs). IsHNP treatment effectively targeted PD-1-expressing CD4 and CD8 T cells in the splenocytes; additionally, it promoted the production of Foxp3-expressing regulatory T cells, which suppressed the differentiation of helper T cells. IsHNP treatment also inhibited anti-CD3 antibody-mediated activation of CD4 and CD8 T cells in mice in vivo. This treatment protected mice from multi-organ inflammation induced by the adoptive transfer of naïve T cells to recombination-activating gene 1 knockout mice. The results of this study imply the therapeutic potential of IsHNPs in the treatment of multi-organ inflammation and other inflammatory diseases.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doenças Autoimunes
/
Nanopartículas
Limite:
Animals
Idioma:
En
Revista:
Biomaterials
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Coréia do Sul
País de publicação:
HOLANDA
/
HOLLAND
/
NETHERLANDS
/
NL
/
PAISES BAJOS
/
THE NETHERLANDS