Homeostatic NF-κB Signaling in Steady-State Migratory Dendritic Cells Regulates Immune Homeostasis and Tolerance
| Autor: | Myriam Baratin, Emeline Pollet, Julien Maurizio, Olivier Demaria, Toby Lawrence, Hiroaki Azukizawa, Suzel Davanture, Adriana Flores-Langarica, Chloe Foray, Marc Dalod, Mohamed Habbeddine, Christophe Verthuy |
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| Rok vydání: | 2015 |
| Předmět: |
Regulatory T cell
Immunology Autoimmunity chemical and pharmacologic phenomena Inflammation Biology medicine.disease_cause Autoantigens T-Lymphocytes Regulatory Immune tolerance Mice Immune system Cell Movement Immunity Immune Tolerance medicine Animals Homeostasis Immunology and Allergy Gene Regulatory Networks Transcription factor Skin Mice Knockout Gene Expression Profiling NF-kappa B hemic and immune systems Dendritic Cells Microarray Analysis I-kappa B Kinase Infectious Diseases medicine.anatomical_structure Gene Expression Regulation Cancer research Lymph Nodes medicine.symptom Signal transduction Spleen Signal Transduction |
| Zdroj: | Immunity. 42:627-639 |
| ISSN: | 1074-7613 |
| Popis: | SummaryMigratory non-lymphoid tissue dendritic cells (NLT-DCs) transport antigens to lymph nodes (LNs) and are required for protective immune responses in the context of inflammation and to promote tolerance to self-antigens in steady-state. However, the molecular mechanisms that elicit steady-state NLT-DC maturation and migration are unknown. By comparing the transcriptome of NLT-DCs in the skin with their migratory counterparts in draining LNs, we have identified a novel NF-κB-regulated gene network specific to migratory DCs. We show that targeted deletion of IKKβ in DCs, a major activator of NF-κB, prevents NLT-DC accumulation in LNs and compromises regulatory T cell conversion in vivo. This was associated with impaired tolerance and autoimmunity. NF-κB is generally considered the prototypical pro-inflammatory transcription factor, but this study describes a role for NF-κB signaling in DCs for immune homeostasis and tolerance that could have implications in autoimmune diseases and immunity. |
| Databáze: | OpenAIRE |
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