Alternative NF-κB signaling controls peripheral homeostasis and function of regulatory T cells.
Immunobiology
; 224(5): 687-696, 2019 09.
Article
em En
| MEDLINE
| ID: mdl-31200979
Regulatory T cells (Tregs) maintain immune homeostasis and play an important role in tissue regeneration after injury. Mutations affecting development or homeostasis of Tregs lead to immune pathologies in humans and are often fatal in mouse models. Although the pathways required for Treg development are being increasingly characterized, factors crucial for Treg homeostasis are not completely understood. Previously we have found a role for alternative NF-κB pathway in restricting T cell activation and Th17 differentiation. Here, by using the mouse model of uncontrolled alternative NF-κB signaling we identify a crucial intrinsic role of RelB signaling in regulating homeostasis and competitive fitness of Tregs. The failure of p100-/- Tregs to maintain the population of effector Tregs and efficiently suppress immune reactions results in lethal multiorgan Th1-mediated inflammation in Rag1-/- recipients. This inflammation is combined with severe lymphopenia and could be rescued by adoptive transfer of wild type Tregs. Thus in addition to its role in Th17 differentiation, RelB acts as a potent inhibitor of Treg effector functions. Our results point to RelB as a potential therapeutic target for Treg manipulation.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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NF-kappa B
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Linfócitos T Reguladores
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Homeostase
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article