title: Immunogenicity is preferentially induced in sparse dendritic cell cultures.
abstract: We have previously shown that human monocyte-derived dendritic cells (DCs) acquired different characteristics in dense or sparse cell cultures. Sparsity promoted the development of IL-12 producing migratory DCs, whereas dense cultures increased IL-10 production. Here we analysed whether the density-dependent endogenous breaks could modulate DC-based vaccines. Using murine bone marrow-derived DC models we show that sparse cultures were essential to achieve several key functions required for immunogenic DC vaccines, including mobility to draining lymph nodes, recruitment and massive proliferation of antigen-specific CD4+ T cells, in addition to their TH1 polarization. Transcription analyses confirmed higher commitment in sparse cultures towards T cell activation, whereas DCs obtained from dense cultures up-regulated immunosuppressive pathway components and genes suggesting higher differentiation plasticity towards osteoclasts. Interestingly, we detected a striking up-regulation of fatty acid and cholesterol biosynthesis pathways in sparse cultures, suggesting an important link between DC immunogenicity and lipid homeostasis regulation.
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Aikaterini
authors.initials: A
authors.lastname: Nasi
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Vishnu Priya
authors.initials: VP
authors.lastname: Bollampalli
authors.affiliation: Department of Medicine, Karolinska University Hospital and Karolinska Institutet, Solna, Sweden.
authors.forename: Meng
authors.initials: M
authors.lastname: Sun
authors.affiliation: Department of Medicine, Science for Life Laboratory, Karolinska Institutet, Solna, Sweden.
authors.forename: Yang
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Amu
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Susanne
authors.initials: S
authors.lastname: Nylén
authors.affiliation: Department of Medicine, Karolinska University Hospital and Karolinska Institutet, Solna, Sweden.
authors.forename: Liv
authors.initials: L
authors.lastname: Eidsmo
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Antonio Gigliotti
authors.initials: AG
authors.lastname: Rothfuchs
authors.affiliation: Department of Medicine, Karolinska University Hospital and Karolinska Institutet, Solna, Sweden.
authors.forename: Bence
authors.initials: B
authors.lastname: Réthi
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002452:Cell Count; D018929:Cell Culture Techniques; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005260:Female; D000071497:Immunogenicity, Vaccine; D008297:Male; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism