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In these pathological conditions, selective silencing of activated T cells through physiological receptors they express remains a clinical challenge. In our previous studies we found that\u00a0activation of\u00a0dopamine receptors (DRs) in resting human T cells activates these cells, and induces by itself many beneficial\u00a0T cell functions.\u00a0In this study, we found that normal human T cells express all types of <jats:styled-content style=\"fixed-case\">DR<\/jats:styled-content>s, and that expression of D1R, D4R and D5R increases profoundly after T cell receptor (TCR) activation. Interestingly, <jats:styled-content style=\"fixed-case\">DR<\/jats:styled-content> agonists shift the membrane potential (<jats:italic>V<\/jats:italic><jats:sub>m<\/jats:sub>) of both resting and activated human T cells, and induces\u00a0instantaneous\u00a0T cell depolarization within 15\u00a0seconds\u00a0only.\u00a0Thus, activation of DRs in T cells depolarize these immune cells, alike activation of DRs in neural cells. The skin of Psoriasis patients contains 20\u2010fold more D1R<jats:sup>+<\/jats:sup> T cells than healthy human\u00a0skin. In line with that, 25\u2010fold more D1R<jats:sup>+<\/jats:sup> T cells are present in Psoriasis humanized mouse model. Highly selective D1\u2010like receptor agonists, primarily Fenoldopam\u00a0(Corlopam) \u2013 a\u00a0D1\u2010like receptor agonist and a drug used in hypertension, induced the following suppressive effects on activated T cells of Psoriasis patients: reduced chemotactic migration towards the chemokine <jats:styled-content style=\"fixed-case\">SDF<\/jats:styled-content>\u20101\/<jats:styled-content style=\"fixed-case\">CXCL<\/jats:styled-content>12; reduced dramatically the secretion of eight cytokines: tumor necrosis factor\u2010<jats:italic>\u03b1<\/jats:italic>, interferon\u2010<jats:italic>\u03b3<\/jats:italic>, interleukin\u20101<jats:italic>\u03b2<\/jats:italic> (<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101<jats:italic>\u03b2<\/jats:italic>), <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20102, <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20104, <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20106, <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20108 and <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201010; and reduced three T cell activation proteins\/markers: <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>69, <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>28 and <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20102. Next, we invented a novel topical\/dermal Fenoldopam formulation, allowing it to be spread\u00a0on, and providing prolonged and regulated release in,\u00a0diseased skin. Our novel topical\/dermal Fenoldopam: reduced secretion of the eight cytokines by activated human T cells; reduced <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101<jats:italic>\u03b2<\/jats:italic> and <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20106 secretion by human lipopolysaccharide\u2010inflamed skin; eliminated preferentially &gt;90% of live and large\/proliferating human T cells. Together, our findings show for the first time that both resting and activated\u00a0T cells are depolarized instantaneously via <jats:styled-content style=\"fixed-case\">DR<\/jats:styled-content>s, and that targeting D1\u2010like receptors in activated T cells and inflamed human skin by Fenoldopam, in Psoriasis, and potentially in other T cell\u2010mediated diseases, could be therapeutic. Validation <jats:italic>in vivo<\/jats:italic> is required.<\/jats:p>","DOI":"10.1111\/imm.13109","type":"journal-article","created":{"date-parts":[[2019,8,19]],"date-time":"2019-08-19T13:05:01Z","timestamp":1566219901000},"page":"171-193","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Instantaneous depolarization of T cells via dopamine receptors, and inhibition of activated T cells of Psoriasis patients and inflamed human skin, by D1\u2010like receptor agonist: Fenoldopam"],"prefix":"10.1111","volume":"158","author":[{"given":"Aviad","family":"Keren","sequence":"first","affiliation":[{"name":"Skin Research Laboratory Faculty of Medicine Technion\u00a0\u2013\u00a0Israel Institute of Technology Haifa Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amos","family":"Gilhar","sequence":"additional","affiliation":[{"name":"Skin Research Laboratory Faculty of Medicine 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