Proteomics profiling of CD4 + T-cell-derived exosomes from patients with rheumatoid arthritis

Int Immunopharmacol. 2023 Sep:122:110560. doi: 10.1016/j.intimp.2023.110560. Epub 2023 Jul 7.

Abstract

Objectives: Our study profiled the CD4 + T-cell-derived exosomes from patients with rheumatoid arthritis (RA) using proteomics.

Methods: Proteomic analysis of CD4 + T-cell-derived exosomes was performed by tandem mass tags (TMT) combined with LC-MS/MS. We validated the most significantly upregulated and downregulated proteins using ELISA and WB.

Results: The proteomic results showed that there were 3 upregulated differentially expressed proteins and 31 downregulated differentially expressed proteins in the RA group. The results indicated that dihydropyrimidinase-related protein 3 (DPYSL3) was significantly upregulated in CD4 + T-cell-derived exosomes, whereas proteasome activator complex subunit 1 (PSME1) was significantly downregulated in the RA group. Bioinformatics analysis showed that proteins were enriched in "positive regulation of gene expression", "antigen processing and presentation", "acute-phase response" and "PI3K-AKT signaling" pathways. ELISA verified that compared to the control group, the RA group showed significant upregulation of DPYSL3, and downregulation of PSME1 in CD4 + T-cell-derived exosomes.

Conclusions: The proteomic analysis results of CD4 + T-cell-derived exosomes from patients with RA suggest that these differentially expressed proteins may be involved in RA pathogenesis. DPYSL3 and PSME1 may become useful biomarkers for RA.

Keywords: Biomarker; CD4+ T cell; Exosome; Proteomic analysis; Rheumatoid arthritis.

MeSH terms

  • Arthritis, Rheumatoid*
  • CD4-Positive T-Lymphocytes
  • Chromatography, Liquid
  • Exosomes* / metabolism
  • Humans
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proteomics
  • Tandem Mass Spectrometry

Substances

  • Phosphatidylinositol 3-Kinases