Lupus & antiphospholipid syndrome

Type I interferon limits interleukin-6 signalling in systemic lupus erythematosus (SLE) through shedding interleukin-6 receptors

Rheumatology (Oxford)Published Mechanistic study

Authors' conclusion

The combination of IL-6 and type I IFN induces shedding of CD126 to sIL-6R, shifting IL-6 signalling to trans-signalling.

Study context

Population
SLE patients and healthy individuals (sera and peripheral blood mononuclear cells (PBMCs)); HepG2 liver cells and transfected HEK-293 T cells
Comparison
SLE patients vs healthy individuals; cell stimulation with IL-6 plus IFNα
Methodological detailsin vitro cell stimulation, ELISA, flow cytometry, immunoprecipitation and western blotting
  • In vitro cell stimulation
  • ELISA
  • Flow cytometry
  • Immunoprecipitation and western blotting

Main finding

As reported in the abstract

  • sIL-6R and IL-6 increased with SLE activity
  • CD126 positive lymphocytes decreased in SLE
  • IL-6 plus IFNα decreased CD126 on lymphocytes but increased sIL-6R in their supernatant
  • IL-6 plus IFNα on HepG2 liver cells resulted in a similar sIL-6R increase
  • Increased supernatant sIL-6R in HEK-293 T cells transfected with wild type CD126, not with the shedding-resistant mutant
  • STAT3 phosphorylation upon IL-6 stimulation reduced

Original publication

Type I interferon limits interleukin-6 signalling in SLE through shedding interleukin-6 receptors. Rheumatology (Oxford). Published 9 July 2025. doi:10.1093/rheumatology/keaf281

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