Format

Send to

Choose Destination
Immunity. 2015 Apr 21;42(4):627-39. doi: 10.1016/j.immuni.2015.03.003. Epub 2015 Apr 7.

Homeostatic NF-κB Signaling in Steady-State Migratory Dendritic Cells Regulates Immune Homeostasis and Tolerance.

Author information

1
Centre d'Immunologie de Marseille-Luminy (CIML), Aix-Marseille Université, UM2, 13288 Marseille, France; Institut National de la Santé et de la Recherche Médicale (INSERM), U1104, 13288 Marseille, France; Centre National de la Recherche Scientifique (CNRS), UMR7280, 13288 Marseille, France.
2
Osaka University, Osaka 565-0871, Japan.
3
IBR-MRC Centre for Immune Regulation, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
4
Centre d'Immunologie de Marseille-Luminy (CIML), Aix-Marseille Université, UM2, 13288 Marseille, France; Institut National de la Santé et de la Recherche Médicale (INSERM), U1104, 13288 Marseille, France; Centre National de la Recherche Scientifique (CNRS), UMR7280, 13288 Marseille, France. Electronic address: lawrence@ciml.univ-mrs.fr.

Abstract

Migratory 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.

PMID:
25862089
DOI:
10.1016/j.immuni.2015.03.003
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center