Sodium Chloride Aggravates Arthritis via Th17 Polarization

Abstract

PurposeSodium chloride (NaCl) has been proposed as a driving factor in autoimmune diseases through the induction of pathogenic CD4+ T helper cells that produce interleukin-17 (Th17 cells). This study investigated the effects of NaCl on inflammatory arthritis in mice and humans.Materials and MethodsCollagen-induced arthritis (CIA) mice were fed a normal or high-salt diet ad libitum, and clinical and histologic features of arthritis were evaluated. The proportion of Th17 cells in the spleens of CIA mice fed a normal or high-salt diet was evaluated by flow cytometry, and the expression of IL-17 in joints and intestines was determined by immunohistochemical staining. We also analyzed the effect of NaCl on Th17 differentiation from peripheral blood monocytes of patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and evaluated the contents of sodium and IL-17 in the synovial fluid of RA and OA patients.ResultsNaCl increased murine and human Th17 cell differentiation in a dose-dependent manner. Clinical and histological arthritis was more severe in the high-salt-fed CIA mice, compared to control CIA mice. The proportion of Th17 cells among splenocytes was higher in CIA mice fed a high-salt diet. Expression of synovial and intestinal IL-17 was also higher in high-salt-fed CIA mice. Comparison of synovial fluid between RA patients and OA patients revealed that Na+ and IL-17 were more abundant in RA synovial fluid.ConclusionThis study suggests that NaCl can aggravate arthritis by affecting Th17 differentiation. Accordingly, limiting salt intake may be helpful for treating inflammatory arthritis, such as RA.

Salt generates antiinflammatory Th17 cells but amplifies pathogenicity in proinflammatory cytokine microenvironments

“…To demonstrate that these NaCl-induced T cell cytokine expression profiles translate into either pro-or anti-inflammatory T cell effector functions, we validated them in vivo. Previously, a pathogenic effect of NaCl has been emphasized for autoimmune diseases in mouse models, which had been based on disease aggravation following a high NaCl diet (18,22,23,(56)(57)(58).…”

Dietary Salt Administration Decreases Enterotoxigenic Bacteroides fragilis (ETBF)-Promoted Tumorigenesis via Inhibition of Colonic Inflammation

“…Other investigators also showed that HSD causes IL-17A-dependent colon inflammation [34]. In several studies using autoimmune disease models, HSD increased the Th17 immune response via the serum/glucocorticoid-regulated kinase (SGK1) differentiation of Th17 cells [16,[35][36][37]. Given those studies, our initial hypothesis was that HSD would increase ETBF-induced tumorigenesis via enhancement of the Th17 immune response.…”

Microbial orchestra in juvenile idiopathic arthritis: Sounds of disarray?

“…It emerged that key regulators of IL‐23 production, including the nuclear factor of activated T cells and the serum glucocorticoid kinase, are regulated by sodium concentration . Additionally, animal data demonstrate that high salt intake can result in worsening of inflammatory conditions, including models of multiple sclerosis, IBD, and RA . In humans, salt intake can modulate the Th17 polarization of T cells .…”

“…152 In humans, salt intake can modulate the Th17 polarization of T cells. 152,153 To our knowledge, there are no trials exclusively evaluating the impact of low-sodium diets, although EEN and anti-inflammatory diets used in IBD 137,138 are low in sodium content.…”

“…Additionally, animal data demonstrate that high salt intake can result in worsening of inflammatory conditions, including models of multiple sclerosis, IBD, and RA . In humans, salt intake can modulate the Th17 polarization of T cells . To our knowledge, there are no trials exclusively evaluating the impact of low‐sodium diets, although EEN and anti‐inflammatory diets used in IBD are low in sodium content.…”