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CD83 orchestrates immunity toward self and non-self in dendritic cells.

Authors
  • Wild, Andreas B1
  • Krzyzak, Lena1
  • Peckert, Katrin1
  • Stich, Lena1
  • Kuhnt, Christine1
  • Butterhof, Alina1
  • Seitz, Christine1
  • Mattner, Jochen2
  • Grüner, Niklas2
  • Gänsbauer, Maximilian2
  • Purtak, Martin2
  • Soulat, Didier2
  • Winkler, Thomas H3
  • Nitschke, Lars3
  • Zinser, Elisabeth1
  • Steinkasserer, Alexander1
  • 1 Department of Immune Modulation and.
  • 2 Institute of Microbiology - Clinical Microbiology, Immunology and Hygiene, Universitätsklinikum Erlangen and Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany. , (Germany)
  • 3 Division of Genetics, Department of Biology, Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany. , (Germany)
Type
Published Article
Journal
JCI Insight
Publisher
American Society for Clinical Investigation
Publication Date
Oct 17, 2019
Volume
4
Issue
20
Identifiers
DOI: 10.1172/jci.insight.126246
PMID: 31527313
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Dendritic cells (DCs) are crucial to balance protective immunity and autoimmune inflammatory processes. Expression of CD83 is a well-established marker for mature DCs, although its physiological role is still not completely understood. Using a DC-specific CD83-conditional KO (CD83ΔDC) mouse, we provide new insights into the function of CD83 within this cell type. Interestingly, CD83-deficient DCs produced drastically increased IL-2 levels and displayed higher expression of the costimulatory molecules CD25 and OX40L, which causes superior induction of antigen-specific T cell responses and compromises Treg suppressive functions. This also directly translates into accelerated immune responses in vivo. Upon Salmonella typhimurium and Listeria monocytogenes infection, CD83ΔDC mice cleared both pathogens more efficiently, and CD83-deficient DCs expressed increased IL-12 levels after bacterial encounter. Using the experimental autoimmune encephalomyelitis model, autoimmune inflammation was dramatically aggravated in CD83ΔDC mice while resolution of inflammation was strongly reduced. This phenotype was associated with increased cell influx into the CNS accompanied by elevated Th17 cell numbers. Concomitantly, CD83ΔDC mice had reduced Treg numbers in peripheral lymphoid organs. In summary, we show that CD83 ablation on DCs results in enhanced immune responses by dysregulating tolerance mechanisms and thereby impairing resolution of inflammation, which also demonstrates high clinical relevance.

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