The pro-inflammatory potential of T cells in juvenile-onset systemic lupus erythematosus

Lucy E Ballantine, Joanne Ong, Angela Midgley, Louise Watson, Brian F Flanagan, Michael W Beresford, Lucy E Ballantine, Joanne Ong, Angela Midgley, Louise Watson, Brian F Flanagan, Michael W Beresford

Abstract

Background: T cells are important to systemic lupus erythematosus (SLE) disease progression. This study determined the pro-inflammatory potential of T cells within the rare condition juvenile-onset SLE (JSLE).

Method: IL-17A and Th1/Th2-related cytokine concentrations were measured in plasma/serum from JSLE patients (n = 19, n = 11) and HC (n = 18, n = 7). IL17A, RORC, IL23 and IL23R mRNA were measured in peripheral blood mononuclear cells (PBMCs) from JSLE and healthy controls (HC) (n = 12). Th17-associated cytokine expression was analysed in the supernatant of CD3/CD28 activated JSLE (n = 7) and HC (n = 6) PBMCs.

Results: JSLE plasma IL-17A level (21.5 ± 5.2 pg/ml) was higher compared to HC (7.2 ± 2.5 pg/ml, p = 0.028). No differences were found in Th1/Th2 cytokines levels. IL = 17A (p = 0.022), IL-6 (p = 0.028) and IL-21 (p = 0.003) concentrations were increased in supernatants from activated JSLE PBMCs. IL-17 F (p = 0.50) and IL-22 (p = 0.43) were also increased but were not statistically significant. IL17A and IL23 mRNA was significantly higher in JSLE PBMCs (p = 0.018 and p = 0.01).

Conclusion: JSLE T cells have an increased ability to secrete Th17 associated cytokines once activated, which could contribute to the pro-inflammatory disease phenotype seen in these patients.

Figures

Figure 1
Figure 1
Cytokines measurement in JSLE patient plasma and serum. (A) IL-17A was measured in plasma from 19 JSLE patients (n = 19; BILAG -2004, A/B = 10; Score, mean (range) 3.1 (0–11)) and 18 healthy controls. JSLE patient levels were significantly higher IL-17A plasma levels compared to healthy controls p = 0.028. (B) PBMCs were isolated from JSLE (n = 12; BILAG -2004, A/B = 6; Score, mean (range) 2.9 (0–8)) and control (n = 12) patients, all genes are expressed relative to the housekeeping gene RPL13A. IL17A, IL23R, RORC and IL23 mRNA were higher in JSLE PBMCs compared to control with IL17A and IL23 mRNA level reaching statistical significance (p = 0.018 and p = 0.01). Data are shown as the mean ± SEM and a Mann–Whitney U test was performed to determine significance values.
Figure 2
Figure 2
IL-17A and Th17 associated cytokine measurement of the cell culture supernatant from CD3/CD28 activated PBMCs. (A) PBMCs from JSLE (n = 7) and control (n = 6) patients were stimulated for 2 days using CD3/CD28 activation beads and IL-17A levels measured in culture supernatants. JSLE patients had a significantly increased level of IL-17A secretion (p = 0.022). (B) Cell culture supernatants from JSLE (n = 9) and control (n = 10) stimulated PBMCs were analysed by bioplex for Th17 associated cytokines. The cytokine IL-6 which is associated with the generation of Th17 cells from naïve T cells was increased in JSLE PBMCs compared to controls (p = 0.028). Cytokines produced by Th17 cells such as IL-17 F (p = 0.50), IL-21 (p = 0.003) and IL-22 (p = 0.43) were also increased in JSLE PBMCs compared to controls. Data are shown as the mean ± SEM and a Mann–Whitney U test was performed to determine significance values.

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