IL-10-producing regulatory B cells exhibit functional defects and play a protective role in severe endotoxic shock.
Pharmacol Res
; 148: 104457, 2019 10.
Article
em En
| MEDLINE
| ID: mdl-31536782
ABSTRACT
Dysregulated host immune homeostasis in sepsis is life-threatening even after a successfully treated bacterial infection. Lipopolysaccharide (LPS) is an endotoxin that is a major contributor to the aberrant immune responses and endotoxic shock in gram-negative bacterial sepsis. However, the current knowledge of the role of B cells in endotoxic shock is limited. Here, we report that CD1d expression in B cells and the percentage of CD5+CD1dhi regulatory B (Breg) cells decreased in a mouse model of endotoxic shock. Interestingly, IL-10 but not FasL expression in CD5+CD1dhi Breg cells in response to endotoxin was dramatically reduced in severe septic shock mice, and the regulatory function of CD5+CD1dhi Breg cells in vitro to control the Th1 response was also diminished. Adoptive transfer of CD5+CD1dhi Breg cells from healthy WT mice but not IL-10 deficient mice downregulated the IFN-γ secretion in CD4+ T cells and conferred protection against severe endotoxic shock in vivo. Our findings demonstrate the change and notable therapeutic potential of IL-10-producing Breg cells in endotoxic shock.
Palavras-chave
5(6)-CFDA N-succinimidyl ester (CFSE, PubChem, CID: 71314542); CD1d; CD4(+) T cells; Endotoxic shock; Eosin (PubChem CID: 11048); Haematoxylin (PubChem CID: 442514); IL-10; Ionomycin (PubChem CID: 6912226); Lipopolysaccharide (PubChem CID: 11970143); Monensin (PubChem CID: 441145); Phorbol 12-myristate 13-acetate (PMA, PubChem CID: 27924); Regulatory B cells
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Choque Séptico
/
Interleucina-10
/
Linfócitos B Reguladores
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article