The Expression of P2X7 Receptor on Th1, Th17, and Regulatory T Cells in Patients with Systemic Lupus Erythematosus or Rheumatoid Arthritis and Its Correlations with Active Disease

Abstract

P2X7 receptor (P2X7R) is highly expressed on immune cells, triggering the release of cytokines and regulating autoimmune responses. To investigate P2X7R surface expression on T helper (Th) 1, Th17, and regulatory T (Treg) cells in patients with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA) and correlations with disease activity, 29 SLE and 29 RA patients and 18 healthy controls (HCs) were enrolled. We showed that SLE and RA patients had significantly higher levels of plasma cytokines (IFN-g, IL-1b, IL-6, IL-17A, and IL-23), frequencies of Th1 and Th17 cells, and expression of P2X7R on Th1 and Th17 than HCs, and the Th17/Treg ratio was significantly increased, whereas Treg cell levels were significantly decreased. The Ca 2+ influx increase following BzATP stimulation was significantly higher in CD4 + PBMCs from SLE and RA patients than in HCs. Blood levels of shed P2X7R were increased in SLE and RA patients. Furthermore, 28-joint Disease Activity Score and SLE Disease Activity Index score showed negative correlations with Treg cell levels and positive correlations with Th17/Treg ratio and Th17 cell P2X7R expression. Interestingly, Th17 cell P2X7R expression was closely correlated with IL-1b, C-reactive protein, the erythrocyte sedimentation rate, anticyclic citrullinated peptide Abs, albumin, and C4. These data indicate that increased Th17 cell P2X7R expression is functionally and positively related to disease activity and some inflammatory mediators in SLE and RA patients, and P2X7R could be critical in promoting the Th17 immune response and contributing to the complex pathogenesis of SLE and RA.

Blood MALT1, Th1, and Th17 cells are dysregulated, inter‐correlated, and correlated with disease activity in rheumatoid arthritis patients; meanwhile, MALT1 decline during therapy relates to treatment outcome

“…Some studies indicate that Th17 cells are positively related to DAS28 of RA patients, while Th1 cells have no correlation with disease activity of RA 37‐39 . Besides, there is no study exploring the relationship between MALT1 and disease activity of RA patients.…”

“…Some studies indicate that Th17 cells are positively related to DAS28 of RA patients, while Th1 cells have no correlation with disease activity of RA. 37 , 38 , 39 Besides, there is no study exploring the relationship between MALT1 and disease activity of RA patients. Partially in line with previous studies, we found that MALT1, Th1, and Th17 cells were all positively correlated with disease activity of RA patients; nonetheless, the correlation coefficients of Th1 cells and RA disease activity related indexes were relatively weak.…”

Mitochondria as Key Players in the Pathogenesis and Treatment of Rheumatoid Arthritis

“…A recent study found that significantly elevated proportions of circulating Th17 and Th1 cells stained positive for P2X7 in samples from either SLE or RA patients compared with healthy controls. The percentage of P2X7-expressing Th17 cells correlated with both DAS28 and serum concentrations of IL-1β ( 184 ). Activation of the P2X7 receptor and NLRP3-dependent IL-1β production by dendritic cells is important for priming of T cells, and this pathway was shown to regulate CD8+ T cell activity in the anti-cancer immune response ( 185 ) and Th17 differentiation in arthritis models ( 181 ).…”

A Variant of sNASP Exacerbates Lymphocyte Subset Disorder and Nephritis in a Spontaneous Lupus Model Sle1.Yaa Mouse

“…T cells have been found to play a crucial role in the pathogenesis of SLE [ 12 , 13 ], among which CD4 + T cells are active mediators for the pathogenesis of SLE [ 13 , 14 ]. Cytokine dysregulation promotes immune dysfunction, and tissue inflammation is one of the hallmarks of SLE [ 15 , 16 ].…”