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Skin Sodium Accumulates in Psoriasis and Reflects Disease Severity

  • Author Footnotes
    24 These authors contributed equally to this work.
    András Maifeld
    Footnotes
    24 These authors contributed equally to this work.
    Affiliations
    Experimental and Clinical Research Center, Charité - Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine, Berlin, Germany

    German Centre for Cardiovascular Research (DZHK), Berlin, Germany

    Berlin Institute of Health, Charité - Universitätsmedizin Berlin, Berlin, Germany

    Charité - Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
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  • Author Footnotes
    24 These authors contributed equally to this work.
    Johannes Wild
    Footnotes
    24 These authors contributed equally to this work.
    Affiliations
    Center of Cardiology - Cardiology I, University Medical Center, Johannes Gutenberg-University Mainz, Mainz, Germany

    Center for Thrombosis and Hemostasis (CTH), University Medical Center, Johannes Gutenberg-University Mainz, Mainz, Germany
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  • Tine V. Karlsen
    Affiliations
    Department of Biomedicine, University of Bergen, Bergen, Norway
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  • Natalia Rakova
    Affiliations
    Experimental and Clinical Research Center, Charité - Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine, Berlin, Germany
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  • Elisa Wistorf
    Affiliations
    Experimental and Clinical Research Center, Charité - Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine, Berlin, Germany
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  • Peter Linz
    Affiliations
    Institute of Radiology, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany

    Department of Nephrology and Hypertension, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany
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  • Rebecca Jung
    Affiliations
    Center for Thrombosis and Hemostasis (CTH), University Medical Center, Johannes Gutenberg-University Mainz, Mainz, Germany

    Institute for Molecular Medicine, University Medical Center, Johannes Gutenberg-University Mainz, Mainz, Germany
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  • Anna Birukov
    Affiliations
    Experimental and Clinical Research Center, Charité - Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine, Berlin, Germany

    German Centre for Cardiovascular Research (DZHK), Berlin, Germany

    Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany

    German Center for Diabetes Research (DZD), Neuherberg, Germany
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  • Author Footnotes
    25 Department of Dermatology, Venereology and Allergology, Charité - Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
    Vladimir-Andrey Gimenez-Rivera
    Footnotes
    25 Department of Dermatology, Venereology and Allergology, Charité - Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
    Affiliations
    IntegraSkin GmbH i.G., Tübingen, Germany
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  • Nicola Wilck
    Affiliations
    Experimental and Clinical Research Center, Charité - Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine, Berlin, Germany

    German Centre for Cardiovascular Research (DZHK), Berlin, Germany

    Berlin Institute of Health, Charité - Universitätsmedizin Berlin, Berlin, Germany

    Department of Nephrology and Internal Intensive Care Medicine, Charité - Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
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  • Theda Bartolomaeus
    Affiliations
    Experimental and Clinical Research Center, Charité - Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine, Berlin, Germany

    German Centre for Cardiovascular Research (DZHK), Berlin, Germany

    Charité - Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
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  • Ralf Dechend
    Affiliations
    Experimental and Clinical Research Center, Charité - Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine, Berlin, Germany

    German Centre for Cardiovascular Research (DZHK), Berlin, Germany

    Berlin Institute of Health, Charité - Universitätsmedizin Berlin, Berlin, Germany

    Charité - Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany

    Helios Clinic Berlin-Buch, Berlin, Germany
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  • Markus Kleinewietfeld
    Affiliations
    VIB Laboratory of Translational Immunomodulation, VIB Center for Inflammation Research (IRC), Hasselt University Campus Diepenbeek, Hasselt, Belgium
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  • Sofia K. Forslund
    Affiliations
    Experimental and Clinical Research Center, Charité - Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine, Berlin, Germany

    German Centre for Cardiovascular Research (DZHK), Berlin, Germany

    Berlin Institute of Health, Charité - Universitätsmedizin Berlin, Berlin, Germany

    Charité - Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
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  • Andreas Krause
    Affiliations
    Medical Centre for Rheumatology and Clinical Immunology, Immanuel Krankenhaus Berlin, Berlin, Germany
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  • Georgios Kokolakis
    Affiliations
    Department of Dermatology, Venereology and Allergology, Charité - Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
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  • Sandra Philipp
    Affiliations
    Department of Dermatology, Venereology and Allergology, Charité - Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
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  • Björn E. Clausen
    Affiliations
    Department of Nephrology and Hypertension, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany
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  • Anna Brand
    Affiliations
    Department of Nephrology and Hypertension, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany
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  • Ari Waisman
    Affiliations
    Department of Nephrology and Hypertension, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany
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  • Florian C. Kurschus
    Affiliations
    Department of Dermatology, Heidelberg University Hospital, Heidelberg, Germany
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  • Joanna Wegner
    Affiliations
    Department of Dermatology, University Medical Center, Johannes Gutenberg-University Mainz, Mainz, Germany
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  • Michael Schultheis
    Affiliations
    Department of Dermatology, University Medical Center, Johannes Gutenberg-University Mainz, Mainz, Germany
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  • Friedrich C. Luft
    Affiliations
    Experimental and Clinical Research Center, Charité - Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine, Berlin, Germany
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  • Michael Boschmann
    Affiliations
    Experimental and Clinical Research Center, Charité - Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine, Berlin, Germany

    Berlin Institute of Health, Charité - Universitätsmedizin Berlin, Berlin, Germany

    Charité - Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
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  • Marcus Kelm
    Affiliations
    Berlin Institute of Health, Charité - Universitätsmedizin Berlin, Berlin, Germany

    Institute for Imaging Science and Computational Modelling in Cardiovascular Medicine, Charité - Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany

    Department of Congenital Heart Disease, German Heart Center Berlin (DHZB), Berlin, Germany
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  • Helge Wiig
    Affiliations
    Department of Biomedicine, University of Bergen, Bergen, Norway
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  • Titus Kuehne
    Affiliations
    Institute for Imaging Science and Computational Modelling in Cardiovascular Medicine, Charité - Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany

    Department of Congenital Heart Disease, German Heart Center Berlin (DHZB), Berlin, Germany
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  • Author Footnotes
    24 These authors contributed equally to this work.
    Dominik N. Müller
    Footnotes
    24 These authors contributed equally to this work.
    Affiliations
    Experimental and Clinical Research Center, Charité - Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine, Berlin, Germany

    German Centre for Cardiovascular Research (DZHK), Berlin, Germany

    Berlin Institute of Health, Charité - Universitätsmedizin Berlin, Berlin, Germany

    Charité - Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany

    Max Delbrück Center for Molecular Medicine in the Helmholtz Association Berlin, Berlin, Germany
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  • Author Footnotes
    24 These authors contributed equally to this work.
    Susanne Karbach
    Footnotes
    24 These authors contributed equally to this work.
    Affiliations
    Center of Cardiology - Cardiology I, University Medical Center, Johannes Gutenberg-University Mainz, Mainz, Germany

    Center for Thrombosis and Hemostasis (CTH), University Medical Center, Johannes Gutenberg-University Mainz, Mainz, Germany
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  • Author Footnotes
    24 These authors contributed equally to this work.
    Lajos Markó
    Correspondence
    Correspondence: Lajos Markó, Experimental and Clinical Research Center, Charité - Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine, Lindenberger Weg 80, 13125 Berlin, Germany.
    Footnotes
    24 These authors contributed equally to this work.
    Affiliations
    Experimental and Clinical Research Center, Charité - Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine, Berlin, Germany

    German Centre for Cardiovascular Research (DZHK), Berlin, Germany

    Berlin Institute of Health, Charité - Universitätsmedizin Berlin, Berlin, Germany

    Charité - Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
    Search for articles by this author
  • Author Footnotes
    24 These authors contributed equally to this work.
    25 Department of Dermatology, Venereology and Allergology, Charité - Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
      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.

      Abbreviations:

      23Na (Sodium-23), IMQ (imiquimod), K (keratin), MRI (magnetic resonance imaging), NaCl (sodium chloride), Th (T helper), TNCB (2,4,6 trinitrochlorobenzene)
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      References

        • Aguiar S.L.F.
        • Miranda M.C.G.
        • Guimarães M.A.F.
        • Santiago H.C.
        • Queiroz C.P.
        • Cunha P.D.S.
        • et al.
        High-salt diet induces IL-17-dependent gut inflammation and exacerbates colitis in mice.
        Front Immunol. 2018; 8: 1969
        • Barton S.P.
        • Abdullah M.S.
        • Marks R.
        Quantification of microvascular changes in the skin in patients with psoriasis.
        Br J Dermatol. 1992; 126: 569-574
        • Binger K.J.
        • Gebhardt M.
        • Heinig M.
        • Rintisch C.
        • Schroeder A.
        • Neuhofer W.
        • et al.
        High salt reduces the activation of IL-4- and IL-13-stimulated macrophages.
        J Clin Invest. 2015; 125: 4223-4238
        • Blauvelt A.
        T-helper 17 cells in psoriatic plaques and additional genetic links between IL-23 and psoriasis.
        J Invest Dermatol. 2008; 128: 1064-1067
        • Cai Y.
        • Fleming C.
        • Yan J.
        New insights of T cells in the pathogenesis of psoriasis.
        Cell Mol Immunol. 2012; 9: 302-309
        • Cai Y.
        • Shen X.
        • Ding C.
        • Qi C.
        • Li K.
        • Li X.
        • et al.
        Pivotal role of dermal IL-17-producing γδ T cells in skin inflammation [published correction appears in Immunity 2011;35:649].
        Immunity. 2011; 35: 596-610
        • Capon F.
        • Burden A.D.
        • Trembath R.C.
        • Barker J.N.
        Psoriasis and other complex trait dermatoses: from loci to functional pathways.
        J Invest Dermatol. 2012; 132: 915-922
        • Chua R.A.
        • Arbiser J.L.
        The role of angiogenesis in the pathogenesis of psoriasis.
        Autoimmunity. 2009; 42: 574-579
        • Croxford A.L.
        • Karbach S.
        • Kurschus F.C.
        • Wörtge S.
        • Nikolaev A.
        • Yogev N.
        • et al.
        IL-6 regulates neutrophil microabscess formation in IL-17A-driven psoriasiform lesions.
        J Invest Dermatol. 2014; 134: 728-735
        • Dahlmann A.
        • Dörfelt K.
        • Eicher F.
        • Linz P.
        • Kopp C.
        • Mössinger I.
        • et al.
        Magnetic resonance-determined sodium removal from tissue stores in hemodialysis patients.
        Kidney Int. 2015; 87: 434-441
        • El Malki K.
        • Karbach S.H.
        • Huppert J.
        • Zayoud M.
        • Reissig S.
        • Schüler R.
        • et al.
        An alternative pathway of imiquimod-induced psoriasis-like skin inflammation in the absence of interleukin-17 receptor a signaling.
        J Invest Dermatol. 2013; 133: 441-451
        • Esser P.R.
        • Martin S.F.
        Pathomechanisms of contact sensitization.
        Curr Allergy Asthma Rep. 2017; 17: 83
        • Grundin T.G.
        • Roomans G.M.
        • Forslind B.
        • Lindberg M.
        • Werner Y.
        X-ray microanalysis of psoriatic skin.
        J Invest Dermatol. 1985; 85: 378-380
        • Hawkes J.E.
        • Gudjonsson J.E.
        • Ward N.L.
        The snowballing literature on imiquimod-induced skin inflammation in mice: a critical appraisal.
        J Invest Dermatol. 2017; 137: 546-549
        • Hernandez A.L.
        • Kitz A.
        • Wu C.
        • Lowther D.E.
        • Rodriguez D.M.
        • Vudattu N.
        • et al.
        Sodium chloride inhibits the suppressive function of FOXP3+ regulatory T cells.
        J Clin Invest. 2015; 125: 4212-4222
        • Jantsch J.
        • Schatz V.
        • Friedrich D.
        • Schröder A.
        • Kopp C.
        • Siegert I.
        • et al.
        Cutaneous Na+ storage strengthens the antimicrobial barrier function of the skin and boosts macrophage-driven host defense.
        Cell Metab. 2015; 21: 493-501
        • Jung S.M.
        • Kim Y.
        • Kim J.
        • Jung H.
        • Yi H.
        • Rim Y.A.
        • et al.
        Sodium chloride aggravates arthritis via Th17 polarization.
        Yonsei Med J. 2019; 60: 88-97
        • Kagami S.
        • Rizzo H.L.
        • Lee J.J.
        • Koguchi Y.
        • Blauvelt A.
        Circulating Th17, Th22, and Th1 cells are increased in psoriasis.
        J Invest Dermatol. 2010; 130: 1373-1383
        • Karbach S.
        • Croxford A.L.
        • Oelze M.
        • Schüler R.
        • Minwegen D.
        • Wegner J.
        • et al.
        Interleukin 17 drives vascular inflammation, endothelial dysfunction, and arterial hypertension in psoriasis-like skin disease.
        Arterioscler Thromb Vasc Biol. 2014; 34: 2658-2668
        • Kitada K.
        • Daub S.
        • Zhang Y.
        • Klein J.D.
        • Nakano D.
        • Pedchenko T.
        • et al.
        High salt intake reprioritizes osmolyte and energy metabolism for body fluid conservation.
        J Clin Invest. 2017; 127: 1944-1959
        • Kleinewietfeld M.
        • Manzel A.
        • Titze J.
        • Kvakan H.
        • Yosef N.
        • Linker R.A.
        • et al.
        Sodium chloride drives autoimmune disease by the induction of pathogenic TH17 cells.
        Nature. 2013; 496: 518-522
        • Kopp C.
        • Beyer C.
        • Linz P.
        • Dahlmann A.
        • Hammon M.
        • Jantsch J.
        • et al.
        Na+ deposition in the fibrotic skin of systemic sclerosis patients detected by 23Na-magnetic resonance imaging [published correction appears in Rheumatology (Oxford) 2017;56:674].
        Rheumatology (Oxford). 2017; 56: 556-560
        • Kopp C.
        • Linz P.
        • Dahlmann A.
        • Hammon M.
        • Jantsch J.
        • Müller D.N.
        • et al.
        23Na magnetic resonance imaging-determined tissue sodium in healthy subjects and hypertensive patients.
        Hypertension. 2013; 61: 635-640
        • Kopp C.
        • Linz P.
        • Maier C.
        • Wabel P.
        • Hammon M.
        • Nagel A.M.
        • et al.
        Elevated tissue sodium deposition in patients with type 2 diabetes on hemodialysis detected by 23Na magnetic resonance imaging.
        Kidney Int. 2018; 93: 1191-1197
        • Kopp C.
        • Linz P.
        • Wachsmuth L.
        • Dahlmann A.
        • Horbach T.
        • Schöfl C.
        • et al.
        (23)Na magnetic resonance imaging of tissue sodium.
        Hypertension. 2012; 59: 167-172
        • Kurschus F.C.
        • Moos S.
        IL-17 for therapy.
        J Dermatol Sci. 2017; 87: 221-227
        • Lerchl K.
        • Rakova N.
        • Dahlmann A.
        • Rauh M.
        • Goller U.
        • Basner M.
        • et al.
        Agreement between 24-hour salt ingestion and sodium excretion in a controlled environment.
        Hypertension. 2015; 66: 850-857
        • Lowes M.A.
        • Russell C.B.
        • Martin D.A.
        • Towne J.E.
        • Krueger J.G.
        The IL-23/T17 pathogenic axis in psoriasis is amplified by keratinocyte responses.
        Trends Immunol. 2013; 34: 174-181
        • Machnik A.
        • Dahlmann A.
        • Kopp C.
        • Goss J.
        • Wagner H.
        • van Rooijen N.
        • et al.
        Mononuclear phagocyte system depletion blocks interstitial tonicity-responsive enhancer binding protein/vascular endothelial growth factor C expression and induces salt-sensitive hypertension in rats.
        Hypertension. 2010; 55: 755-761
        • Machnik A.
        • Neuhofer W.
        • Jantsch J.
        • Dahlmann A.
        • Tammela T.
        • Machura K.
        • et al.
        Macrophages regulate salt-dependent volume and blood pressure by a vascular endothelial growth factor-C-dependent buffering mechanism.
        Nat Med. 2009; 15: 545-552
        • Mähler A.
        • Balogh A.
        • Csizmadia I.
        • Klug L.
        • Kleinewietfeld M.
        • Steiniger J.
        • et al.
        Metabolic, mental and immunological effects of normoxic and hypoxic training in multiple sclerosis patients: a pilot study.
        Front Immunol. 2018; 9: 2819
        • Matthias J.
        • Maul J.
        • Noster R.
        • Meinl H.
        • Chao Y.Y.
        • Gerstenberg H.
        • et al.
        Sodium chloride is an ionic checkpoint for human TH2 cells and shapes the atopic skin microenvironment.
        Sci Transl Med. 2019; 11eaau0683
        • McKenzie D.R.
        • Kara E.E.
        • Bastow C.R.
        • Tyllis T.S.
        • Fenix K.A.
        • Gregor C.E.
        • et al.
        IL-17-producing γδ T cells switch migratory patterns between resting and activated states.
        Nat Commun. 2017; 8: 15632
        • Mehta N.N.
        • Azfar R.S.
        • Shin D.B.
        • Neimann A.L.
        • Troxel A.B.
        • Gelfand J.M.
        Patients with severe psoriasis are at increased risk of cardiovascular mortality: cohort study using the General Practice Research Database.
        Eur Heart J. 2010; 31: 1000-1006
        • Nast A.
        • Amelunxen L.
        • Augustin M.
        • Boehncke W.H.
        • Dressler C.
        • Gaskins M.
        • et al.
        S3 guideline for the treatment of psoriasis vulgaris, update - short version part 1 - systemic treatment.
        J Dtsch Dermatol Ges. 2018; 16: 645-669
        • Neimann A.L.
        • Shin D.B.
        • Wang X.
        • Margolis D.J.
        • Troxel A.B.
        • Gelfand J.M.
        Prevalence of cardiovascular risk factors in patients with psoriasis.
        J Am Acad Dermatol. 2006; 55: 829-835
        • Nickoloff B.J.
        Characterization of lymphocyte-dependent angiogenesis using a SCID mouse: human skin model of psoriasis.
        J Investig Dermatol Symp Proc. 2000; 5: 67-73
        • O'Brien R.L.
        • Born W.K.
        Dermal γδ T cells--what have we learned?.
        Cell Immunol. 2015; 296: 62-69
        • Reich K.
        • Armstrong A.W.
        • Langley R.G.
        • Flavin S.
        • Randazzo B.
        • Li S.
        • et al.
        Guselkumab versus secukinumab for the treatment of moderate-to-severe psoriasis (ECLIPSE): results from a phase 3, randomised controlled trial.
        Lancet. 2019; 394: 831-839
        • Roth S.
        • Markó L.
        • Birukov A.
        • Hennemuth A.
        • Kühnen P.
        • Jones A.
        • et al.
        Tissue sodium content and arterial hypertension in obese adolescents.
        J Clin Med. 2019; 8: 2036
        • Schatz V.
        • Neubert P.
        • Schröder A.
        • Binger K.
        • Gebhard M.
        • Müller D.N.
        • et al.
        Elementary immunology: Na+ as a regulator of immunity.
        Pediatr Nephrol. 2017; 32: 201-210
        • Schneider M.P.
        • Raff U.
        • Kopp C.
        • Scheppach J.B.
        • Toncar S.
        • Wanner C.
        • et al.
        Skin sodium concentration correlates with left ventricular hypertrophy in CKD.
        J Am Soc Nephrol. 2017; 28: 1867-1876
        • Schön M.P.
        • Erpenbeck L.
        The interleukin-23/interleukin-17 axis links adaptive and innate immunity in psoriasis.
        Front Immunol. 2018; 9: 1323
        • Schüler R.
        • Brand A.
        • Klebow S.
        • Wild J.
        • Veras F.P.
        • Ullmann E.
        • et al.
        Antagonization of IL-17A attenuates skin inflammation and vascular dysfunction in mouse models of psoriasis.
        J Invest Dermatol. 2019; 139: 638-647
        • Sutton C.E.
        • Lalor S.J.
        • Sweeney C.M.
        • Brereton C.F.
        • Lavelle E.C.
        • Mills K.H.
        Interleukin-1 and IL-23 induce innate IL-17 production from gammadelta T cells, amplifying Th17 responses and autoimmunity.
        Immunity. 2009; 31: 331-341
        • Szabó G.
        • Magyar Z.
        Electrolyte concentrations in subcutaneous tissue fluid and lymph.
        Lymphology. 1982; 15: 174-177
        • Takeshita J.
        • Wang S.
        • Shin D.B.
        • Mehta N.N.
        • Kimmel S.E.
        • Margolis D.J.
        • et al.
        Effect of psoriasis severity on hypertension control: a population-based study in the United Kingdom.
        JAMA Dermatol. 2015; 151: 161-169
        • Tomalin L.E.
        • Russell C.B.
        • Garcet S.
        • Ewald D.A.
        • Klekotka P.
        • Nirula A.
        • et al.
        Short-term transcriptional response to IL-17 receptor-A antagonism in the treatment of psoriasis.
        J Allergy Clin Immunol. 2020; 145: 922-932
        • Toussirot E.
        • Béreau M.
        • Vauchy C.
        • Saas P.
        Could sodium chloride be an environmental trigger for immune-mediated diseases? An overview of the experimental and clinical evidence.
        Front Physiol. 2018; 9: 440
        • van der Fits L.
        • Mourits S.
        • Voerman J.S.
        • Kant M.
        • Boon L.
        • Laman J.D.
        • et al.
        Imiquimod-induced psoriasis-like skin inflammation in mice is mediated via the IL-23/IL-17 axis.
        J Immunol. 2009; 182: 5836-5845
        • Wagner E.F.
        • Schonthaler H.B.
        • Guinea-Viniegra J.
        • Tschachler E.
        Psoriasis: what we have learned from mouse models.
        Nat Rev Rheumatol. 2010; 6: 704-714
        • Waisman A.
        To be 17 again--anti-interleukin-17 treatment for psoriasis [published correction appears in N Engl J Med 2012;367:93].
        N Engl J Med. 2012; 366: 1251-1252
        • Wiig H.
        • Schröder A.
        • Neuhofer W.
        • Jantsch J.
        • Kopp C.
        • Karlsen T.V.
        • et al.
        Immune cells control skin lymphatic electrolyte homeostasis and blood pressure.
        J Clin Invest. 2013; 123: 2803-2815
        • Wilck N.
        • Balogh A.
        • Markó L.
        • Bartolomaeus H.
        • Müller D.N.
        The role of sodium in modulating immune cell function.
        Nat Rev Nephrol. 2019; 15: 546-558
        • Wilck N.
        • Matus M.G.
        • Kearney S.M.
        • Olesen S.W.
        • Forslund K.
        • Bartolomaeus H.
        • et al.
        Salt-responsive gut commensal modulates TH17 axis and disease.
        Nature. 2017; 551: 585-589
        • Willebrand R.
        • Hamad I.
        • Van Zeebroeck L.
        • Kiss M.
        • Bruderek K.
        • Geuzens A.
        • et al.
        High salt inhibits tumor growth by enhancing anti-tumor immunity.
        Front Immunol. 2019; 10: 1141
        • Wohn C.
        • Brand A.
        • van Ettinger K.
        • Brouwers-Haspels I.
        • Waisman A.
        • Laman J.D.
        • et al.
        Gradual development of psoriatic skin lesions by constitutive low-level expression of IL-17A.
        Cell Immunol. 2016; 308: 57-65
        • Wu C.
        • Yosef N.
        • Thalhamer T.
        • Zhu C.
        • Xiao S.
        • Kishi Y.
        • et al.
        Induction of pathogenic TH17 cells by inducible salt-sensing kinase SGK1.
        Nature. 2013; 496: 513-517
        • Zhang W.C.
        • Zheng X.J.
        • Du L.J.
        • Sun J.Y.
        • Shen Z.X.
        • Shi C.
        • et al.
        High salt primes a specific activation state of macrophages, M(Na).
        Cell Res. 2015; 25: 893-910
        • Žurauskas M.
        • Barkalifa R.
        • Alex A.
        • Marjanovic M.
        • Spillman Jr., D.R.
        • Mukherjee P.
        • et al.
        Assessing the severity of psoriasis through multivariate analysis of optical images from non-lesional skin.
        Sci Rep. 2020; 10: 9154