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Quantitative proteomics reveals protein dysregulation during T cell activation in multiple sclerosis patients compared to healthy controls.
Cappelletti, Chiara; Eriksson, Anna; Brorson, Ina Skaara; Leikfoss, Ingvild S; Kråbøl, Oda; Høgestøl, Einar August; Vitelli, Valeria; Mjaavatten, Olav; Harbo, Hanne F; Berven, Frode; Bos, Steffan D; Berge, Tone.
Afiliação
  • Cappelletti C; Department of Mechanical, Electronics and Chemical Engineering, Faculty of Technology, Art and Design, OsloMet-Oslo Metropolitan University, Postboks 4, St. Olavs Plass, 0130, Oslo, Norway.
  • Eriksson A; Institute of Clinical Medicine, Medical Faculty, University of Oslo, Oslo, Norway.
  • Brorson IS; Institute of Clinical Medicine, Medical Faculty, University of Oslo, Oslo, Norway.
  • Leikfoss IS; Department of Neurology, Oslo University Hospital, Ullevål, Postboks 4950, 0424 Nydalen, Oslo, Norway.
  • Kråbøl O; Institute of Clinical Medicine, Medical Faculty, University of Oslo, Oslo, Norway.
  • Høgestøl EA; Department of Neurology, Oslo University Hospital, Ullevål, Postboks 4950, 0424 Nydalen, Oslo, Norway.
  • Vitelli V; Neuroscience Research Unit, Department of Research, Innovation and Education, Oslo University Hospital, Oslo, Norway.
  • Mjaavatten O; Institute of Clinical Medicine, Medical Faculty, University of Oslo, Oslo, Norway.
  • Harbo HF; Department of Neurology, Oslo University Hospital, Ullevål, Postboks 4950, 0424 Nydalen, Oslo, Norway.
  • Berven F; Department of Psychology, Faculty of Social Sciences, University of Oslo, Oslo, Norway.
  • Bos SD; Oslo Centre for Biostatistics and Epidemiology, Department of Biostatistics, University of Oslo, Oslo, Norway.
  • Berge T; Proteomics Unit at University of Bergen (PROBE), Department of Biomedicine, University of Bergen, Postboks 7804, 5020, Bergen, Norway.
Clin Proteomics ; 19(1): 23, 2022 Jul 05.
Article em En | MEDLINE | ID: mdl-35790914
BACKGROUND: Multiple sclerosis (MS) is an autoimmune, neurodegenerative disorder with a strong genetic component that acts in a complex interaction with environmental factors for disease development. CD4+ T cells are pivotal players in MS pathogenesis, where peripherally activated T cells migrate to the central nervous system leading to demyelination and axonal degeneration. Through a proteomic approach, we aim at identifying dysregulated pathways in activated T cells from MS patients as compared to healthy controls. METHODS: CD4+ T cells were purified from peripheral blood from MS patients and healthy controls by magnetic separation. Cells were left unstimulated or stimulated in vitro through the TCR and costimulatory CD28 receptor for 24 h prior to sampling. Electrospray liquid chromatography-tandem mass spectrometry was used to measure protein abundances. RESULTS: Upon T cell activation the abundance of 1801 proteins was changed. Among these proteins, we observed an enrichment of proteins expressed by MS-susceptibility genes. When comparing protein abundances in T cell samples from healthy controls and MS patients, 18 and 33 proteins were differentially expressed in unstimulated and stimulated CD4+ T cells, respectively. Moreover, 353 and 304 proteins were identified as proteins exclusively induced upon T cell activation in healthy controls and MS patients, respectively and dysregulation of the Nur77 pathway was observed only in samples from MS patients. CONCLUSIONS: Our study highlights the importance of CD4+ T cell activation for MS, as proteins that change in abundance upon T cell activation are enriched for proteins encoded by MS susceptibility genes. The results provide evidence for proteomic disturbances in T cell activation in MS, and pinpoint to dysregulation of the Nur77 pathway, a biological pathway known to limit aberrant effector T cell responses.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Ano de publicação: 2022 Tipo de documento: Article