A20 expression in dendritic cells protects mice from LPS‐induced mortality

• DOI: 10.1002/eji.201444795
• Publication Date: 2014-12-05T14:55:50Z
• Authors: Nguyen Thi Xuan; Xu Wang; Gopala Nishanth; Ari Waisman; Katrin Borucki; Berend Isermann; Michael Naumann; Martina Deckert; Dirk Schlüter
• Keywords: CD11c

DCs contribute to immune homeostasis under physiological conditions and regulate the activation during infection. The deubiquitinase A20 inhibits of NF-κB-dependent reactions, prevents hyperactivation steady-state conditions. However, role DC-specific pathological is unknown. Here, we demonstrate that upon injection low-dose LPS, mice with deletion (CD11c-Cre A20(fl/fl) ) died within 6 h, whereas controls survived. LPS-induced mortality in CD11c-Cre was characterized by increased serum levels IL-2, IL-10, IL-12, IFN-γ, TNF. Upon LPS stimulation, NF-κB ERK-NFATc3 pathways were enhanced A20-deficient DCs, resulting an production TNF both vitro vivo. Targeted inhibition ERK abolished IL-2. failed induce tolerance, which independent T cells intestinal flora, since T-cell depletion decolonization could not prevent death LPS-challenged mice. In conclusion, these findings show preserves also required for tolerance.