Lupus & antiphospholipid syndrome

Induction of interleukin 21 receptor expression via enhanced intracellular metabolism in B cells and its relevance to the disease activity in systemic lupus erythematosus

RMD OpenPublished Mechanistic study

Authors' conclusion

IL-21R mRNA-GAPDH binding dissociation associated with rapid glycolytic enhancement by the TLR9 ligand in B cells may induce plasmocyte differentiation through IL-21 signals and be involved in exacerbating SLE.

Study context

Population
Peripheral blood B cells from healthy controls and systemic lupus erythematosus (SLE) patients
Comparison
SLE patients vs healthy controls; CpG stimulation of B cells
Outcome
Intracellular metabolism and IL-21R expression in B cells
Methodological detailsin vitro
  • In vitro

Main finding

As reported in the abstract

  • CpG (TLR9 ligand) induced enhanced IL-21R expression in CD19+CD27- cells after 24 hours
  • Adding IL-21 to CpG enhanced the extracellular acidification rate (glycolysis) within 30 min
  • CpG-induced IL-21R expression selectively inhibited by 2-deoxy-D-glucose (HK2 inhibitor) and heptelidic acid (GAPDH inhibitor)
  • CpG stimulation dissociated the binding between IL-21R messenger RNA (mRNA) and GAPDH present under no stimulation
  • HK2 and GAPDH expression higher in CD19+CD27- cells of lupus patients than healthy controls
  • GAPDH expression correlated with plasmocyte count and disease activity score

Original publication

Induction of interleukin 21 receptor expression via enhanced intracellular metabolism in B cells and its relevance to the disease activity in systemic lupus erythematosus. RMD Open. Published 31 December 2024. doi:10.1136/rmdopen-2024-004567

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