title: Dendritic cell-secreted lipocalin2 induces CD8+ T-cell apoptosis, contributes to T-cell priming and leads to a TH1 phenotype.
abstract: Lipocalin 2 (LCN2), which is highly expressed by dendritic cells (DCs) when treated with dexamethasone (Dex) and lipopolysaccharide (LPS), plays a key role in the defence against bacteria and is also involved in the autocrine apoptosis of T-cells. However, the function of LCN2 when secreted by DCs is unknown: this is a critical gap in our understanding of the regulation of innate and adaptive immune systems. Tolerance, stimulation and suppression are functions of DCs that facilitate the fine-tuning of the immune responses and which are possibly influenced by LCN2 secretion. We therefore examined the role of LCN2 in DC/T-cell interaction. WT or Lcn2-/- bone marrow-derived DCs were stimulated with LPS or LPS+IFN-γ with and without Dex and subsequently co-cultured with T-cells from ovalbumin-specific TCR transgenic (OT-I and OT-II) mice. We found that CD8+ T-cell apoptosis was highly reduced when Lcn2-/- DCs were compared with WT. An in vivo CTL assay, using LPS-treated DCs, showed diminished killing ability in mice that had received Lcn2-/- DCs compared with WT DCs. As a consequence, we analysed T-cell proliferation and found that LCN2 participates in T-cell-priming in a dose-dependent manner and promotes a TH1 microenvironment. DC-secreted LCN2, whose function has previously been unknown, may in fact have an important role in regulating the balance between TH1 and TH2. Our results yield insights into DC-secreted LCN2 activity, which could play a pivotal role in cellular immune therapy and in regulating immune responses.
authors.affiliation: Laboratory of Tumour Immunology, St. Anna Children's Cancer Research Institute, Vienna, Austria.
authors.forename: Melanie
authors.initials: M
authors.lastname: Floderer
authors.affiliation: Institute of Pharmacology and Toxicology, Department for Biomedical Science, University of Veterinary Medicine Vienna, Vienna, Austria.
authors.forename: Michaela
authors.initials: M
authors.lastname: Prchal-Murphy
authors.affiliation: Laboratory of Tumour Immunology, St. Anna Children's Cancer Research Institute, Vienna, Austria.
authors.forename: Caterina
authors.initials: C
authors.lastname: Vizzardelli
mesh_terms: D000209:Acute-Phase Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D060833:Cellular Microenvironment / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D007114:Immunization; D007371:Interferon-gamma / Q000494:pharmacology; D000071068:Lipocalin-2; D054834:Lipocalins / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D015513:Oncogene Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D018417:Th1 Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology
chemical_list: D000209:Acute-Phase Proteins; D016207:Cytokines; D000071068:Lipocalin-2; D054834:Lipocalins; D008070:Lipopolysaccharides; D015513:Oncogene Proteins; C071332:Lcn2 protein, mouse; D007371:Interferon-gamma