title: E2-2 Dependent Plasmacytoid Dendritic Cells Control Autoimmune Diabetes.
abstract: Autoimmune diabetes is a consequence of immune-cell infiltration and destruction of pancreatic β-cells in the islets of Langerhans. We analyzed the cellular composition of the insulitic lesions in the autoimmune-prone non-obese diabetic (NOD) mouse and observed a peak in recruitment of plasmacytoid dendritic cells (pDCs) to NOD islets around 8-9 weeks of age. This peak coincides with increased spontaneous expression of type-1-IFN response genes and CpG1585 induced production of IFN-α from NOD islets. The transcription factor E2-2 is specifically required for the maturation of pDCs, and we show that knocking out E2-2 conditionally in CD11c+ cells leads to a reduced recruitment of pDCs to pancreatic islets and reduced CpG1585 induced production of IFN-α during insulitis. As a consequence, insulitis has a less aggressive expression profile of the Th1 cytokine IFN-γ and a markedly reduced diabetes incidence. Collectively, these observations demonstrate a disease-promoting role of E2-2 dependent pDCs in the pancreas during autoimmune diabetes in the NOD mouse.
authors.affiliation: Department of Immunology and Microbiology, University of Copenhagen, Copehagen, Denmark.|Department of Experimental Medical Science, Section of Immunology, Lund University, Lund, Sweden.
authors.forename: Lisbeth
authors.initials: L
authors.lastname: Hansen
authors.affiliation: Department of Experimental Medical Science, Section of Immunology, Lund University, Lund, Sweden.
authors.forename: Anja
authors.initials: A
authors.lastname: Schmidt-Christensen
authors.affiliation: Department of Immunology and Microbiology, University of Copenhagen, Copehagen, Denmark.|Department of Experimental Medical Science, Section of Immunology, Lund University, Lund, Sweden.
authors.forename: Shashank
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Department of Immunology and Microbiology, University of Copenhagen, Copehagen, Denmark.|Department of Experimental Medical Science, Section of Immunology, Lund University, Lund, Sweden.
authors.forename: Nina
authors.initials: N
authors.lastname: Fransén-Pettersson
authors.affiliation: Department of Immunology and Microbiology, University of Copenhagen, Copehagen, Denmark.|Department of Experimental Medical Science, Section of Immunology, Lund University, Lund, Sweden.
authors.forename: Tine D
authors.initials: TD
authors.lastname: Hannibal
authors.affiliation: Department of Microbiology and Immunology, Columbia Medical Center, Columbia University, New York, NY, United States of America.
authors.forename: Boris
authors.initials: B
authors.lastname: Reizis
authors.affiliation: Julia McFarlane Diabetes Research Centre (JMDRC) and Department of Microbiology, Immunology and Infectious Diseases, Snyder Institute for Chronic Diseases, University of Calgary, AB T2N 1N4, Canada.|Institut D'Investigacions Biomediques August Pi i Sunyer, Barcelona, Spain.
authors.forename: Pere
authors.initials: P
authors.lastname: Santamaria
authors.affiliation: Department of Immunology and Microbiology, University of Copenhagen, Copehagen, Denmark.|Department of Experimental Medical Science, Section of Immunology, Lund University, Lund, Sweden.
authors.forename: Dan
authors.initials: D
authors.lastname: Holmberg
mesh_terms: D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000378:metabolism*; D003713:Dendritic Cells / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D005260:Female; D016898:Interferon-alpha / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D010179:Pancreas / Q000378:metabolism; D000073940:Transcription Factor 4; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D016898:Interferon-alpha; C090743:Tcf4 protein, mouse; D000073940:Transcription Factor 4; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma