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Lepper, M.F. ; Ohmayer, U. ; von Toerne, C. ; Maison, N. ; Ziegler, A.-G. ; Hauck, S.M.

Proteomic landscape of patient-derived CD4+T cells in recent-onset type 1 diabetes.

J. Proteome Res. 17, 618-634 (2017)
Postprint DOI PMC
Open Access Green
The pathophysiology underlying the autoimmune disease type 1 diabetes (T1D) is poorly understood. Obtaining an accurate proteomic profile of the T helper cell population is essential for understanding the pathogenesis of T1D. Here, we performed in-depth proteomic profiling of peripheral CD4+ T cells in a pediatric cohort to identify cellular signatures associated with the onset of T1D. Using only 250 000 CD4+ T cells per patient, isolated from biobanked PBMC samples, we identified nearly 6000 proteins using deep-proteome profiling with LC-MS/MS data independent acquisition. Our analysis revealed an inflammatory signature in patients with T1D; this signature is characterized by circulating mediators of neutrophils, platelets, and the complement system. This signature likely reflects the inflammatory extracellular milieu, which suggests that activation of the innate immune system plays an important role in disease onset. Our results emphasize the potential value of using high-resolution LC-MS/MS to investigate limited quantities of biobanked samples to identify disease-relevant proteomic patterns. Proteomic profiles of 114 individuals have been deposited in a comprehensive portable repository serving as a unique resource for CD4+ T cell expression in the context of both health and T1D disease.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Type 1 Diabetes ; Cd4+t Cells ; Proteomic Profiling ; Lc-ms/ms ; Data-independent Acquisition ; Meta-human Spectral Library ; Autoimmune ; Inflammation ; Biomarker ; Neutrophil; Combined Transmembrane Topology; Neutrophil Extracellular Traps; Data-independent Acquisition; Signal Peptide Prediction; Gene-expression; Peripheral-blood; T-cells; Children; Autoimmunity; Risk
Sprache englisch
Veröffentlichungsjahr 2017
HGF-Berichtsjahr 2017
ISSN (print) / ISBN 1535-3893
e-ISSN 1535-3907
Zeitschrift Journal of Proteome Research
Quellenangaben Band: 17, Heft: 1, Seiten: 618-634 Artikelnummer: , Supplement: ,
Verlag American Chemical Society (ACS)
Verlagsort Washington
Begutachtungsstatus Peer reviewed
Institut(e) CF Metabolomics & Proteomics (CF-MPC)
Institute of Asthma and Allergy Prevention (IAP)
Institute of Diabetes Research (IDF)
POF Topic(s) 30203 - Molecular Targets and Therapies
30202 - Environmental Health
30201 - Metabolic Health
Forschungsfeld(er) Enabling and Novel Technologies
Allergy
Helmholtz Diabetes Center
PSP-Element(e) G-505700-001
G-503300-001
G-502100-001
DOI 10.1021/acs.jproteome.7b00712
WOS ID WOS:000419749800056
Scopus ID 85040163087
PubMed ID 29182335
Erfassungsdatum 2017-12-04
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