Systemic sclerosis & Raynaud's

The role of iTr35 cells in the inflammatory response and fibrosis progression of systemic sclerosis

Rheumatology (Oxford)Published Mechanistic study

Authors' conclusion

Both iTr35 and Tr1 cells are involved in SSc-related inflammation and fibrosis. IL-35 can induce iTr35 cells, showing a synergistic effect with IL-10. We also found that iTr35 cells can inhibit T cell proliferation and differentiation via the STAT3/6 signalling pathway, thereby causing fibrosis.

Study context

Population
Patients with SSc
Participants
68 patients
Comparison
SSc patients vs control group
  • SScn = 68
Methodological detailsflow cytometry, ELISA, immunofluorescence, western blot and immunohistochemistry
  • Flow cytometry
  • ELISA
  • Immunofluorescence, western blot and immunohistochemistry

Main finding

As reported in the abstract

  • Peripheral blood: iTr35 cell proportions higher and Tr1 cells lower than control
  • IL-35 expression increased, IL-10 levels decreased
  • Skin fibroblasts: EBI3, IL-12Ap35, Foxp3 and IL-10 decreased; collagen I, TGF-β, α-SMA and fibronectin increased
  • Phosphorylated STAT3/6 increased; iTr35 and Tr1 cell levels significantly decreased
  • CD4+ cells with both rhIL-35 and rhIL-10: more iTr35 and Tr1 cells than with rhIL-35 or rhIL-10 alone
  • Viability of conventional CD4+ T cells decreased with increasing iTr35 cells
  • iTr35 cells affected α-SMA expression through the STAT3/6 signalling pathway

Original publication

The role of iTr35 cells in the inflammatory response and fibrosis progression of systemic sclerosis. Rheumatology (Oxford). Published 3 February 2023. doi:10.1093/rheumatology/kead053

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