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Alternative NF-κB signaling controls peripheral homeostasis and function of regulatory T cells.
Koliesnik, Ievgen O; Andreas, Nico; Thuy, Andreas; Sreekantapuram, Sravya; Haenold, Ronny; Weih, Falk.
Afiliação
  • Koliesnik IO; Leibniz Institute on Aging - Fritz Lipmann Institute (FLI), Jena, Germany. Electronic address: ev.kolesnik@gmail.com.
  • Andreas N; Leibniz Institute on Aging - Fritz Lipmann Institute (FLI), Jena, Germany; Institute of Immunology, University Hospital Jena, Jena, Germany.
  • Thuy A; Center for Sepsis Control and Care (CSCC) and the Center for Molecular Biomedicine (CMB), University Hospital Jena, Germany.
  • Sreekantapuram S; Leibniz Institute on Aging - Fritz Lipmann Institute (FLI), Jena, Germany; Leibniz Institute for Natural Product Research and Infection Biology Hans Knöll Institute, Jena, Germany.
  • Haenold R; Leibniz Institute on Aging - Fritz Lipmann Institute (FLI), Jena, Germany.
  • Weih F; Leibniz Institute on Aging - Fritz Lipmann Institute (FLI), Jena, Germany.
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transdução de Sinais / NF-kappa B / Linfócitos T Reguladores / Homeostase Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transdução de Sinais / NF-kappa B / Linfócitos T Reguladores / Homeostase Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2019 Tipo de documento: Article