Mass Cytometry Reveals Global Immune Remodeling with Multi-lineage Hypersensitivity to Type I Interferon in Down Syndrome.

Adult Down Syndrome / immunology Female Flow Cytometry Humans Interferon-alpha / immunology Male Middle Aged
CyTOF Down syndrome JAK/STAT autoimmunity immune dysregulation inflammation interferon mass cytometry single cell trisomy 21

Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
12 11 2019
Historique:
received: 26 03 2019
revised: 28 08 2019
accepted: 09 10 2019
entrez: 14 11 2019
pubmed: 14 11 2019
medline: 17 9 2020
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1016/j.celrep.2019.10.038 PMID: 31722205 PMC: PMC6871766
pubmed: 31722205
pii: S2211-1247(19)31352-X
doi: 10.1016/j.celrep.2019.10.038
pmc: PMC6871766
mid: NIHMS1542945
pii:
doi:

Substances chimiques

Interferon-alpha 0

Banques de données

ClinicalTrials.gov
['NCT02864108']

Types de publication

Clinical Trial Journal Article Multicenter Study Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

1893-1908.e4

Subventions

Organisme : NCI NIH HHS
ID : T32 CA190216
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM120109
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI150305
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA117907
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002535
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI141662
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI145988
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA046934
Pays : United States
Organisme : NIAMS NIH HHS
ID : K23 AR070897
Pays : United States
Organisme : NIAMS NIH HHS
ID : R61 AR077495
Pays : United States

Informations de copyright

Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.

Auteurs

Katherine A Waugh (KA)

Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.

Paula Araya (P)

Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.

Ahwan 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 Boulder, Boulder, CO 80302, USA.

Kimberly R Jordan (KR)

Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.

Keith P Smith (KP)

Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.

Ross E Granrath (RE)

Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.

Santosh Khanal (S)

Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.

Eric T Butcher (ET)

Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.

Belinda Enriquez Estrada (BE)

Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.

Angela L 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.

Jennifer A McWilliams (JA)

Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.

Ross Minter (R)

Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.

Tiana Dimasi (T)

Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.

Kelley L 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 80045, USA.

Dmitry Baturin (D)

Department of Dermatology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.

Andrew T Pham (AT)

Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.

Matthew D Galbraith (MD)

Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.

Kyle W Bartsch (KW)

Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.

Michael E 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 80045, USA.

Christopher C Porter (CC)

Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.

Kelly D 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 80045, USA.

Elena W 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, Aurora, CO 80045, USA.

Joaquin M 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 Boulder, Boulder, CO 80302, USA. Electronic address: joaquin.espinosa@cuanschutz.edu.

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Mass Cytometry Reveals Global Immune...
questionsmedicales.fr › Malformations et maladies congénitales, héréditaires et néonatales › Maladies génétiques congénitales › Maladies chromosomiques › Syndrome de Down › Mass Cytometry Reveals Global Immune...
questionsmedicales.fr › Techniques d'investigation › Techniques cytologiques › Cytophotométrie › Cytométrie en flux › Mass Cytometry Reveals Global Immune...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Mass Cytometry Reveals Global Immune...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Interférons › Interféron de type I › Interféron alpha › Mass Cytometry Reveals Global Immune...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › Mass Cytometry Reveals Global Immune...