CD4+CD126low/- Foxp3+ Cell Population Represents a Superior Subset of Regulatory T Cells in Treating Autoimmune Diseases.
Mol Ther
; 28(11): 2406-2416, 2020 11 04.
Article
em En
| MEDLINE
| ID: mdl-32738192
ABSTRACT
CD4+Foxp3+ regulatory T (Treg) cells are crucial for maintaining homeostasis and preventing autoimmune diseases. Nonetheless, we and others have previously reported that natural Treg cells are unstable and dysfunctional in the inflamed environment with a high-salt diet, limiting the Treg function in disease control. In this study, we made an innovative observation showing a high degree of heterogeneity within the Treg pool. We identified that CD126, interleukin (IL)-6 receptor alpha chain, contributed to Treg cell instability. Using a series of in vitro and in vivo experimental approaches, we demonstrated that CD126Lo/- Treg cells presented greater function and were more stable than CD126Hi nTreg cells, even in the presence of IL-6 and inflammation. Blockade of programmed death-1 (PD-1) interrupted CD126Lo/- nTreg cell stability. Additionally, CD126Lo/- Treg cells can treat colitis and established collagen-induced arthritis, while the CD126Hi cell population failed to do this. Moreover, we noted that CD126 expression of Treg cells had a positive correlation to rheumatoid arthritis (RA) severity and the stability of Treg cells. Our results strongly suggest that the manipulation of CD126Lo/- nTreg cells could be a novel strategy for the treatment of autoimmune diseases and for other conditions associated with a deficit of Treg cells.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doenças Autoimunes
/
Linfócitos T Reguladores
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Mol Ther
Assunto da revista:
BIOLOGIA MOLECULAR
/
TERAPEUTICA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Peru