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Sodium Chloride Aggravates Arthritis via Th17 Polarization

 Seung Min Jung  ;  Youngkyun Kim  ;  Juryun Kim  ;  Hyerin Jung  ;  Hyoju Yi  ;  Yeri Alice Rim  ;  Narae Park  ;  Seung Ki Kwok  ;  Sung Hwan Park  ;  Ji Hyeon Ju 
 YONSEI MEDICAL JOURNAL, Vol.60(1) : 88-97, 2019-01 
Journal Title
Issue Date
Animals ; Arthritis, Experimental / immunology* ; Arthritis, Experimental / pathology* ; Arthritis, Rheumatoid / drug therapy ; Arthritis, Rheumatoid / pathology ; Cell Differentiation / drug effects ; Cell Polarity* / drug effects ; Humans ; Inflammation / pathology ; Interleukin-17 / biosynthesis ; Intestines / drug effects ; Intestines / pathology ; Male ; Mice ; Sodium Chloride / adverse effects* ; Sodium Chloride, Dietary / adverse effects ; Synovial Fluid / metabolism ; Synovial Membrane / drug effects ; Synovial Membrane / pathology ; Th17 Cells / drug effects ; Th17 Cells / immunology*
Rheumatoid arthritis ; Th17 cells ; collagen-induced arthritis ; salt ; sodium chloride
Purpose: Sodium 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 methods: Collagen-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.

Results: NaCl 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.

Conclusion: This 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.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Jung, SeungMin(정승민) ORCID logo https://orcid.org/0000-0003-3465-2181
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