Autocrine Regulation of Interleukin-3 in the Activity of Regulatory T Cells and its Effectiveness in the Pathophysiology of Sepsis.
J Infect Dis
; 223(5): 893-904, 2021 03 03.
Article
em En
| MEDLINE
| ID: mdl-32702107
ABSTRACT
Regulatory T cells (Tregs) play a crucial role in modulating the inflammatory response and participated in sepsis-related immune dysfunctions. However, little is known about the regulatory mechanisms by which Tregs are kept in check during immune responses. Here, we verified the simultaneous expression of interleukin-3 (IL-3) and its receptor (IL-3R) in Tregs. Then, by modulation of IL-3 expression via lentiviral transduction-mediated small interfering RNA, we demonstrated that IL-3 negatively regulated Tregs activity via an autocrine mechanism. Furthermore, we found that anti-IL-3 antibody treatment significantly diminished inflammatory cytokines and organ injury, and improved survival in septic mice, which was associated with enhanced Treg percentage and function. Collectively, these results suggest that IL-3 negatively regulates the activity of Tregs in a previously unrecognized autocrine manner, and plays an important role in the excessive inflammatory response in sepsis, which might be utilized as a therapeutic strategy for the treatment of complications in sepsis.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Interleucina-3
/
Linfócitos T Reguladores
/
Sepse
Limite:
Animals
Idioma:
En
Revista:
J Infect Dis
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China