Supranutritional selenium suppresses ROS-induced generation of RANKL-expressing osteoclastogenic CD4 T cells and ameliorates rheumatoid arthritis.

OBJECTIVE

The benefit of Se supplementation in rheumatoid arthritis (RA) has been tested in clinical trials, but results remain inconclusive. The objective of this study was to specifically investigate the potential benefit of supranutritional Se by examining human samples from an area with supranutritional Se intake and testing a mouse model of RA.

METHODS

Peripheral blood mononuclear cells (PBMCs) from RA patients ( = 57) and healthy controls (HC,  = 71) from an area of supranutritional Se intake (Enshi, Hubei, China) were analysed by flow cytometry. Serum cytokine and Se levels were measured by cytometric beads array (CBA) and inductively coupled plasma mass spectrometry (ICP-MS), respectively. With sufficient or supranutritional selenium intake, mice were induced with collagen-induced arthritis (CIA) and examined for disease activity and immunopathology. The influence of Se supplementation in the generation of RANKL-expressing osteoclastogenic CD4 T cells was investigated by assays.

RESULTS

In Enshi city, HC showed the above-normal concentrations of serum Se concentrations while RA patients were enriched in the normal range (70-150 ng mL) or below. RA patients with higher Se levels demonstrated milder disease and lower levels of C-reactive protein, IL-6, RANKL and Th17 cells. In the mouse CIA model, supranutritional Se supplementation delayed disease onset, ameliorated joint pathology and reduced CD4CD44RANKL T cells. Se supplementation could suppress RANKL expression in cultured mouse Th17 cells.

CONCLUSION

Supranutritional Se suppresses RANKL-expressing osteoclastogenic CD4 T cells and could be beneficial to RA, which warrants formal testing in randomised clinical trials.