Wang, Xu, Nishanth, Gopala, Waisman, Ari ORCID: 0000-0003-4304-8234, Borucki, Katrin, Isermann, Berend, Naumann, Michael ORCID: 0000-0002-8060-2313, Deckert, Martina and Schlueter, Dirk (2015). A20 expression in dendritic cells protects mice from LPS-induced mortality. Eur. J. Immunol., 45 (3). S. 818 - 829. HOBOKEN: WILEY. ISSN 1521-4141

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Abstract

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

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Wang, XuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nishanth, GopalaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Waisman, AriUNSPECIFIEDorcid.org/0000-0003-4304-8234UNSPECIFIED
Borucki, KatrinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Isermann, BerendUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Naumann, MichaelUNSPECIFIEDorcid.org/0000-0002-8060-2313UNSPECIFIED
Deckert, MartinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schlueter, DirkUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-411681
DOI: 10.1002/eji.201444795
Journal or Publication Title: Eur. J. Immunol.
Volume: 45
Number: 3
Page Range: S. 818 - 829
Date: 2015
Publisher: WILEY
Place of Publication: HOBOKEN
ISSN: 1521-4141
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
NF-KAPPA-B; ACTIVATION; SURVIVAL; TRANSCRIPTION; MACROPHAGES; HOMEOSTASIS; ENDOCYTOSIS; INDUCTION; DEPLETION; RESPONSESMultiple languages
ImmunologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/41168

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