A wave of Foxp3+ regulatory T cell accumulation in the neonatal liver plays unique roles in maintaining self-tolerance.
Cell Mol Immunol
; 17(5): 507-518, 2020 05.
Article
em En
| MEDLINE
| ID: mdl-31171863
ABSTRACT
Newborn animals require tightly regulated local and systemic immune environments to govern the development and maturation of multiple organs/tissues even though the immune system itself is far from mature during the neonatal period. Regulatory T cells (Tregs) are essential for maintaining immune tolerance/homeostasis and modulating inflammatory responses. The features of Tregs in the neonatal liver under steady-state conditions are not well understood. The present study aimed to investigate the phenotype, functions, and significance of neonatal Tregs in the liver. We found a wave of thymus-derived Treg influx into the liver during 1-2 weeks of age. Depletion of these Tregs between days 7 and 11 after birth rapidly resulted in Th1-type liver inflammation and metabolic disorder. More Tregs in the neonatal liver than in the spleen underwent MHC II-dependent activation and proliferation, and the liver Tregs acquired stronger suppressive functions. The transcriptomic profile of these neonatal liver Tregs showed elevated expression of PPARγ and T-bet and features of Tregs that utilize lipid metabolic machinery and are capable of regulating Th1 responses. The accumulation of Tregs with unique features in the neonatal liver is critical to ensure self-tolerance and liver maturation.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T Reguladores
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Fatores de Transcrição Forkhead
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Tolerância Imunológica
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Fígado
Limite:
Animals
Idioma:
En
Revista:
Cell Mol Immunol
Ano de publicação:
2020
Tipo de documento:
Article