000K utf8 1100 $c2020 1500 eng 2050 urn:nbn:de:gbv:8-mods-2020-00457-0 2051 10.3389/fimmu.2020.00661 3000 Parackova, Zuzana 3010 Hasler, Robert 3010 Klocperk, Adam 3010 Petruzelkova, Lenka 3010 Pruhova, Stepanka 3010 Sediva, Anna 3010 Sumnik, Zdenek 3010 Vrabcova, Petra 3010 Zentsova, Irena 4000 Neutrophil Extracellular Trap Induced Dendritic Cell Activation Leads to Th1 Polarization in Type 1 Diabetes [Parackova, Zuzana] 4209 Neutrophils releasing neutrophil extracellular traps (NETs) infiltrate the pancreas prior to type 1 diabetes (T1D) onset; however, the precise nature of their contribution to disease remains poorly defined. To examine how NETs affect immune functions in T1D, we investigated NET composition and their effect on dendritic cells (DCs) and T lymphocytes in T1D children. We showed that T1D patient NET composition differs substantially from that of healthy donors and that the presence of T1D-NETs in a mixed peripheral blood mononuclear cell culture caused a strong shift toward IFNγ-producing T lymphocytes, mediated through activation of innate immunity cells in T1D samples. Importantly, in a monocyte-derived DC (moDC) culture, NETs induced cytokine production, phenotypic change and IFNγ-producing T cells only in samples from T1D patients but not in those from healthy donors. RNA-seq analysis revealed that T1D-NETs presence causes TGFβ downregulation and IFNα upregulation and creates pro-T1D signature in healthy moDCs. 4950 https://doi.org/10.3389/fimmu.2020.00661$xR$3Volltext$534 4950 https://nbn-resolving.org/urn:nbn:de:gbv:8-mods-2020-00457-0$xR$3Volltext$534 4961 https://macau.uni-kiel.de/receive/macau_mods_00000858 5051 610 5550 Autoimmunity 5550 innate immunity 5550 Monocyte-derived Dendritic Cells 5550 Net 5550 Netosis 5550 Neutrophils 5550 type 1 diabetes