Background/Purpose Sodium chloride (NaCl) recently has been shown to drive autoimmune diseases through the induction of pathogenic interleukin 17-producing T helper (Th17) cells. This study investigated the effect of NaCl on Th17 cell differentiation in human and murine arthritis.

Methods To evaluateth in vivo arthritogenic effect of NaCl, collagen-induced arthritis (CIA) mice were fed a normal or high-salt diet ad libitum, and paw swelling was scored visually. Splenocytes were analysed by flow cytometry for RORgt expression, and splenic CD4⁺ T cells were differentiated into Th17 cells. Peripheral blood mononuclear cells obtained from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) were cultured under Th17 cell-differentiating conditions in a high-salt environment and were analysed by flow cytometry to quantify the Th17 cell population.

Results NaCl increased murine and human Th17 cell differentiation in a dose-dependent manner and aggravated arthritis in CIA mice. Joint inflammation was more severe in the high-salt-fed CIA mice. T cells from high-salt-fed CIA mice expressed a higher level of RORgt and were more likely to differentiate into Th17 cells. Th17 cells were located primarily in arthritic joints, and also observed the intestinal tract of high-salt-fed CIA mice. Na⁺ and IL-17 concentrations were higher in synovial fluid from RA patients than in fluid from OA patients. There was a tendency towards increased RORgt expression after NaCl treatment in arthritic patients.

Conclusion This study suggests that NaCl can aggravate arthritis by affecting Th17 differentiation. Limiting salt intake might be helpful in the management of arthritis.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/salt-aggravates-arthritis-by-th17-polarization/