6533b831fe1ef96bd1299863

RESEARCH PRODUCT

Skin Sodium Accumulates in Psoriasis and Reflects Disease Severity

Marcus KelmMarcus KelmAndreas KrausePeter LinzVladimir-andrey Gimenez-riveraFlorian C. KurschusJoanna WegnerAndrás MaifeldElisa WistorfLajos MarkóDominik N. MüllerTheda BartolomaeusTheda BartolomaeusAnna BrandRalf DechendSusanne KarbachGeorgios KokolakisNicola WilckJohannes WildNatalia RakovaAri WaismanTine V. KarlsenMarkus KleinewietfeldSandra PhilippMichael BoschmannMichael BoschmannMichael BoschmannAnna BirukovHelge WiigBjörn E. ClausenSofia K. ForslundMichael SchultheisTitus KuehneFriedrich C. LuftRebecca Jung

subject

Malemedicine.medical_specialtySodiumchemistry.chemical_elementInflammationImiquimodDermatologySodium ChlorideLymphocyte ActivationSeverity of Illness IndexBiochemistryArticleMiceInternal medicinePsoriasismedicineExtracellularAnimalsHumansPsoriasisT helper 17 cellMolecular BiologyCells CulturedSkinintegumentary systembusiness.industrySpectrophotometry AtomicSpectrum AnalysisInterleukin-17SodiumCell DifferentiationCell Biologymedicine.diseasePathophysiologyMice Inbred C57BLEndocrinologychemistryCardiovascular and Metabolic DiseasesTh17 Cellsmedicine.symptombusinessIntracellularmedicine.drug

description

Sodium can accumulate in the skin at concentrations exceeding serum levels. A high sodium environment can lead to pathogenic T helper 17 cell expansion. Psoriasis is a chronic inflammatory skin disease in which IL-17. producing T helper 17 cells play a crucial role. In an observational study, we measured skin sodium content in patients with psoriasis and in age-matched healthy controls by Sodium-23 magnetic resonance imaging. Patients with PASI > 5 showed significantly higher sodium and water content in the skin but not in other tissues than those with lower PASI or healthy controls. Skin sodium concentrations measured by Sodium-23 spectroscopy or by atomic absorption spectrometry in ashed-skin biopsies verified the findings with Sodium-23 magnetic resonance imaging. In vitro T helper 17 cell differentiation of naive CD4(+) cells from patients with psoriasis markedly induced IL-17A expression under increased sodium chloride concentrations. The imiquimod-induced psoriasis mouse model replicated the human findings. Extracellular tracer Chromium-51-EDTA measurements in imiquimod- and sham-treated skin showed similar extracellular volumes, rendering excessive water of intracellular origin. Chronic genetic IL-17A-driven psoriasis mouse models underlined the role of IL-17A in dermal sodium accumulation and inflammation. Our data describe skin sodium as a pathophysiological feature of psoriasis, which could open new avenues for its treatment.

https://doi.org/10.1016/j.jid.2021.06.013