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

First Author  Baratin M Year  2015
Journal  Immunity Volume  42
Issue  4 Pages  627-39
PubMed ID  25862089 Mgi Jnum  J:229701
Mgi Id  MGI:5753017 Doi  10.1016/j.immuni.2015.03.003
Citation  Baratin M, et al. (2015) Homeostatic NF-kappaB Signaling in Steady-State Migratory Dendritic Cells Regulates Immune Homeostasis and Tolerance. Immunity 42(4):627-39
abstractText  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-kappaB-regulated gene network specific to migratory DCs. We show that targeted deletion of IKKbeta in DCs, a major activator of NF-kappaB, prevents NLT-DC accumulation in LNs and compromises regulatory T cell conversion in vivo. This was associated with impaired tolerance and autoimmunity. NF-kappaB is generally considered the prototypical pro-inflammatory transcription factor, but this study describes a role for NF-kappaB signaling in DCs for immune homeostasis and tolerance that could have implications in autoimmune diseases and immunity.
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