Abstract P236: Sodium Accumulates in the Skin of Patients and Mice With Psoriasis

Abstract

Sodium can be buffered in the skin, which mechanism is altered during aging and in certain diseases such as hypertension. High salt environment can promote autoimmunity by expanding pathogenic IL-17 producing T helper (Th17) cells. Psoriasis is a relapsing and remitting inflammatory autoimmune disease affecting the skin and joints and involves proinflammatory Th17 cells. Here we tested the hypothesis if psoriatic skin has a higher sodium content in mice and humans. We used two psoriasis mouse models; the K14-IL-17A ind/+ mice overexpressing IL-17A in K14-positive keratinocytes and the imiquimod (IMQ) mouse model by applying 62.5 mg IMQ cream (5%) on the shaved back and ears of FVB/N mice for 5 days daily. End of the study skins of mice were collected, weighted, dried and ashed to measure water and sodium content. Additionally, skin sodium and water content were measured in psoriasis patients and aged matched healthy controls by non-invasive 23 Na-MRI on non-affected flexor site of the lower leg and by 23 Na-spectroscopy to compare affected and non-affected sites of the leg. K14-IL-17A ind/+ mice had significantly higher sodium content compared to control IL-17A ind/+ mice (0.191±0.021 vs. 0.137±0.023 mg/g dry weight) together with an elevated water content. IMQ-treated back skin had significantly higher sodium content compared to untreated ventral skin of the same mice (0.175±0.023 vs. 0.143±0.014 mg/g dry weight), whereas sham mice had a significantly lower content in both regions (0.116±0.010 vs. 0.107±0.005 mg/g dry weight). IMQ treatment led to significant expansion of IL-17 producing γδT cells in the skin, regional lymph nodes and in the spleen with typical skin lesions. Patients with psoriasis area and severity index (PASI) >5 had significantly higher sodium content in the skin compared to those with lower PASI or with healthy controls (17.73±1.52 vs. 14.32±1.54 vs. 14.30±2.59 AU, respectively); this elevation was water coupled. PASI significantly correlated with skin sodium content (Pearson’s r=0.598, P<0.001). Additionally, patients with PASI>5 has higher sodium content in the affected skin compared to non-affected skin of the same patient. Data from animal models and humans argue for higher sodium accumulation in the inflamed skin.