Anti-fibrotic characteristics of Vγ9+ γδ T cells in systemic sclerosis

Noa Markovits, Anna Bendersky, Ronen Loebstein, Marina Brusel, Efrat Kessler, Ilan Bank

Research output: Contribution to journalArticlepeer-review

Abstract

Objective. γδ T cells of the Vγ9Vd2 subtype secrete anti-fibrotic cytokines upon isopentenyl pyrophosphate (IPP) stimulation. In this study, we sought to compare IPP and Zoledronate, an upregulator of IPP, effects on proliferation and cytokine secretion of Vγ9+ T cells from systemic sclerosis (SSc) patients and healthy controls (HCs). We also examined the effect of IPP-triggered peripheral blood mononuclear cells (PBMC) on fibroblast procollagen secretion. Methods. PBMC from SSc patients and HCs were stimulated by increasing concentrations of Zoledronate, with or without IPP, and Vγ9+ T cell percentages were calculated using FACScan analysis. Subsequently, PBMC were cultured with IPP or toxic shock syndrome toxin-1 (TSST-1), and contents of the anti-fibrotic cytokines tumour necrosis factor (TNF)-α and interferon (IFN)-α were measured by ELISA kits. Finally, supernatants of IPP-triggered Vγ9+ T cells from SSc patients were added to fibroblast cultures, and relative intensities of procollagen a1 chains were determined by densinometry. Results. Higher concentrations of Zoledronate were required for maximal proliferation of Vγ9+ T cells in 9 SSc patients compared to 9 HCs, irrespective of exogenous IPP. When compared to stimulation by TSST-1, a non-Vγ9+ selective reagent, secretion of the antifibrotic cytokines TNF-α and IFN-α in response to IPP was relatively diminished in SSc but not in HCs. Reduction of procollagen secretion by fibroblasts cultured with supernatants of IPPstimulated PBMC was observed only in some SSc patients. Conclusion. Activated Vγ9+ T cells could act as anti- fibrotic mediators in SSc, although decreased responsiveness to IPP may play a role in the pathological fibrosis of this disease.

Original languageEnglish
Pages (from-to)23-29
Number of pages7
JournalClinical and Experimental Rheumatology
Volume34
StatePublished - 2016

Keywords

  • Fibrosis
  • Isopentenyl pyrophosphate
  • Systemic sclerosis
  • Zoledronic acid
  • γδ T cells

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