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Mass Cytometry Reveals Global Immune Remodeling with Multi-lineage Hypersensitivity to Type I Interferon in Down Syndrome.
Waugh, Katherine A; Araya, Paula; Pandey, Ahwan; Jordan, Kimberly R; Smith, Keith P; Granrath, Ross E; Khanal, Santosh; Butcher, Eric T; Estrada, Belinda Enriquez; Rachubinski, Angela L; McWilliams, Jennifer A; Minter, Ross; Dimasi, Tiana; Colvin, Kelley L; Baturin, Dmitry; Pham, Andrew T; Galbraith, Matthew D; Bartsch, Kyle W; Yeager, Michael E; Porter, Christopher C; Sullivan, Kelly D; Hsieh, Elena W; Espinosa, Joaquin M.
Afiliación
  • Waugh KA; Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
  • Araya P; Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
  • Pandey A; Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Molecular, Cellular and Developmental Biology, University of Colorado Bould
  • Jordan KR; Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
  • Smith KP; Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
  • Granrath RE; Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
  • Khanal S; Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
  • Butcher ET; Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
  • Estrada BE; Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
  • Rachubinski AL; Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
  • McWilliams JA; Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
  • Minter R; Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
  • Dimasi T; Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
  • Colvin KL; Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Bioengineering, University of Colorado Anschutz Medical Campus, Aurora, CO 80
  • Baturin D; Department of Dermatology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
  • Pham AT; Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
  • Galbraith MD; Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
  • Bartsch KW; Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
  • Yeager ME; Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Bioengineering, University of Colorado Anschutz Medical Campus, Aurora, CO 80
  • Porter CC; Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.
  • Sullivan KD; Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 8004
  • Hsieh EW; Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Pediatrics, University of Colorado Anschutz Medical Campus,
  • Espinosa JM; Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Molecular, Cellular and Developmental Biology, University of Colorado Bould
Cell Rep ; 29(7): 1893-1908.e4, 2019 11 12.
Article en En | MEDLINE | ID: mdl-31722205
ABSTRACT
People with Down syndrome (DS; trisomy 21) display a different disease spectrum relative to the general population, including lower rates of solid malignancies and higher incidence of neurological and autoimmune conditions. However, the mechanisms driving this unique clinical profile await elucidation. We completed a deep mapping of the immune system in adults with DS using mass cytometry to evaluate 100 immune cell types, which revealed global immune dysregulation consistent with chronic inflammation, including key changes in the myeloid and lymphoid cell compartments. Furthermore, measurement of interferon-inducible phosphorylation events revealed widespread hypersensitivity to interferon-α in DS, with cell-type-specific variations in downstream intracellular signaling. Mechanistically, this could be explained by overexpression of the interferon receptors encoded on chromosome 21, as demonstrated by increased IFNAR1 surface expression in all immune lineages tested. These results point to interferon-driven immune dysregulation as a likely contributor to the developmental and clinical hallmarks of DS.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Interferón-alfa / Síndrome de Down Tipo de estudio: Clinical_trials Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Cell Rep Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Interferón-alfa / Síndrome de Down Tipo de estudio: Clinical_trials Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Cell Rep Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos