Background The pathogenesis of systemic sclerosis (SSc) is largely unknown, although proinflammatory cytokines are considered to play an important role.
Aims Investigate the pattern of expression of proinflammatory cytokines by peripheral blood (PB) Th17 cell and IL-2 and IL-17 relative gene expression in SSc and to explore their clinical associations.
Methods This study included 41 SSc patients and 20 age- and sex-matched healthy controls (HC). SSc patients were classified according to LeRoy et al. as having limited cutaneous SSc (lSSc, n = 29) or diffuse cutaneous SSc (dSSc, n = 12). A further subdivision was made based upon clinical parameters of disease duration and clinical manifestations.
Intracellular expression of IL-17, IL-2, TNF-α and IFN-γ in Th17 cells was assessed by flow cytometry. A detailed functional activity characterisation of Th17 cells was performed in a single multicolour data file obtained after merging the original six-colour-staining (eight-parameter) data files from each sample using the Infinicyt (Cytogonos) software.
Relative gene expression of IL-2 and IL-17 in total PB cells was determined by qRT-PCR
Results No differences were observed concerning the frequency of Th17 cells or Tc17 cells between SSc patients and HC. Th17 cells from both diffuse and limited SSc showed a higher expression of IL-2 (particularly in dSSc) than Th17 cells from HC. Similar observations were made for TNF-α expression but it only reached statistical significance in lSSc. Likewise, an increased frequency of Tc17 cells expressing IL-2 in lSSc was also observed.
Eight distinct Th17 cell subpopulations according to their pattern of cytokine expression (IL-17, IL-2, TNF-α and IFN-γ) were identify after merging data files. A higher frequency of Th17 cells simultaneously producing simultaneously IL17, IL-2 and TNF-α was observed in lSSc. On the other hand a significantly lower frequency of Th17 cells simultaneously producing IL-17, TNF-α and IFN-γ was also observed in the same group. The percentage of Th17 cells producing only TNF-α or IFN-γ was significantly decreased in SSc patients compared to HC group. Moreover a higher IL-17 mRNA expression in total PB cells was observed in SSc patients and no differences were found concerning IL-2 mRNA levels.
Conclusions These results suggest that Th17 cells are functionally altered in SSc patients, exhibiting a higher ability to simultaneously produce IL-17, IL-2 and TNF-α. We also observed in SSc patients increased levels of IL-17 mRNA expression in total PB cells.
These data suggest that Th17 cells may be involved in pathophysiology and/or disease progression of SSc.
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