{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T06:36:55Z","timestamp":1784011015738,"version":"3.55.0"},"reference-count":47,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2023,10,28]],"date-time":"2023-10-28T00:00:00Z","timestamp":1698451200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Sandoz and Almirall","award":["RIBS_RIC_N_COMP_20_01"],"award-info":[{"award-number":["RIBS_RIC_N_COMP_20_01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Psoriasis is a chronic inflammatory skin disease whose molecular mechanisms and microenvironment are poorly understood. We performed gene expression analysis through the nCounter\u00ae PanCancer Immune Profiling Panel (NanoString Technologies, Seattle, WA, USA) on 22 FFPE punch biopsies from 19 psoriasis-affected patients. A subset of five cases was analyzed before (T0) and after 6 months (T6) of treatment with dimethyl fumarate (DMF) to address immune microenvironment changes. Molecular comparisons according to biopsy site and age of onset showed a different distribution of innate immune cells (mast cells, macrophages, NK cells, and DC cells) and pathways (complement regulation and transporter functions). The analysis according to PASI (Psoriasis Area and Severity Index) led to non-significant results, suggesting no link between molecular expression profile and clinical amount of skin disease. In DMF-treated patients, we observed a strong immunomodulatory effect after treatment: A subversion of exhausted CD8 T cells, NK CD56dim cells, Tregs, neutrophils, CD45+ cells, T cells, B cells, and macrophages was reported between the two analyzed time-points, as well as the reduction in pro-inflammatory pathways and molecules, including cytotoxicity, pathogen defense, antigen processing, adhesion, cell cycle, chemokines, cytokines, and interleukins. The inflammatory psoriatic microenvironment can be modulated using DMF with encouraging results, achieving an immune-tolerant and non-inflammatory condition through the regulation of both innate and adaptive immunity.<\/jats:p>","DOI":"10.3390\/jcm12216820","type":"journal-article","created":{"date-parts":[[2023,10,29]],"date-time":"2023-10-29T05:01:08Z","timestamp":1698555668000},"page":"6820","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Exploring Psoriasis Inflammatory Microenvironment by NanoString Technologies"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3989-0501","authenticated-orcid":false,"given":"Alessia Andrea","family":"Ricci","sequence":"first","affiliation":[{"name":"Pathology Unit, Department of Medical Sciences, University of Turin, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Dapavo","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Section of Dermatology, University of Turin, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7386-3219","authenticated-orcid":false,"given":"Luca","family":"Mastorino","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Section of Dermatology, University of Turin, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Roccuzzo","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Section of Dermatology, University of Turin, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samanta","family":"Wolff","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Section of Dermatology, University of Turin, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0098-1406","authenticated-orcid":false,"given":"Simone","family":"Ribero","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Section of Dermatology, University of Turin, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1977-7410","authenticated-orcid":false,"given":"Paola","family":"Cassoni","sequence":"additional","affiliation":[{"name":"Pathology Unit, Department of Medical Sciences, University of Turin, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Senetta","sequence":"additional","affiliation":[{"name":"Pathology Unit, Department of Oncology, University of Turin, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Quaglino","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Section of Dermatology, University of Turin, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Meglio, D., Villanova, F., and Nestle, F.O. (2014). Psoriasis. Cold Spring Harb. Perspect. Med., 4.","DOI":"10.1101\/cshperspect.a015354"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"J314","DOI":"10.1016\/j.jaut.2009.12.001","article-title":"Geoepidemiology and environmental factors of psoriasis and psoriatic arthritis","volume":"34","author":"Chandran","year":"2010","journal-title":"J. Autoimmun."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1111\/j.1365-2133.2006.07675.x","article-title":"A classification of psoriasis vulgaris according to phenotype","volume":"156","author":"Griffiths","year":"2007","journal-title":"Br. J. Dermatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/S0190-9622(85)70188-0","article-title":"Psoriasis of early and late onset: Characterization of two types of psoriasis vulgaris","volume":"13","author":"Henseler","year":"1985","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1016\/S0140-6736(20)32549-6","article-title":"Psoriasis","volume":"397","author":"Griffiths","year":"2021","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"15382","DOI":"10.1038\/ncomms15382","article-title":"Large scale meta-analysis characterizes genetic architecture for common psoriasis associated variants","volume":"8","author":"Tsoi","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1038\/jid.2009.319","article-title":"Molecular dissection of psoriasis: Integrating genetics and biology","volume":"130","author":"Elder","year":"2010","journal-title":"J. Investig. Dermatol."},{"key":"ref_8","first-page":"32","article-title":"Drug-provoked psoriasis: Is it drug induced or drug aggravated? Understanding pathophysiology and clinical relevance","volume":"3","author":"Kim","year":"2010","journal-title":"J. Clin. Aesthet. Dermatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1111\/j.0022-202X.2005.23681.x","article-title":"Cigarette smoking, body mass index, and stressful life events as risk factors for psoriasis: Results from an italian case-control study","volume":"125","author":"Naldi","year":"2005","journal-title":"J. Investig. Dermatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.it.2012.11.005","article-title":"The il-23\/t17 pathogenic axis in psoriasis is amplified by keratinocyte responses","volume":"34","author":"Lowes","year":"2013","journal-title":"Trends Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"m1590","DOI":"10.1136\/bmj.m1590","article-title":"National, regional, and worldwide epidemiology of psoriasis: Systematic analysis and modelling study","volume":"369","author":"Parisi","year":"2020","journal-title":"BMJ"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1016\/j.immuni.2019.03.021","article-title":"The il-17 family of cytokines in health and disease","volume":"50","author":"McGeachy","year":"2019","journal-title":"Immunity"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1016\/S0140-6736(08)60725-4","article-title":"Efficacy and safety of ustekinumab, a human interleukin-12\/23 monoclonal antibody, in patients with psoriasis: 76-week results from a randomised, double-blind, placebo-controlled trial (phoenix 1)","volume":"371","author":"Leonardi","year":"2008","journal-title":"Lancet"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2175","DOI":"10.1038\/jid.2009.65","article-title":"Th17 cytokines stimulate ccl20 expression in keratinocytes in vitro and in vivo: Implications for psoriasis pathogenesis","volume":"129","author":"Harper","year":"2009","journal-title":"J. Investig. Dermatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1016\/S0140-6736(86)91502-3","article-title":"Psoriasis and alpha-interferon","volume":"1","author":"Quesada","year":"1986","journal-title":"Lancet"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/S0952-7915(99)80014-4","article-title":"Antigen presentation by mhc class i and its regulation by interferon gamma","volume":"11","author":"Fruh","year":"1999","journal-title":"Curr. Opin. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1016\/j.celrep.2015.12.072","article-title":"Neutrophil-derived proteases escalate inflammation through activation of il-36 family cytokines","volume":"14","author":"Henry","year":"2016","journal-title":"Cell Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1016\/j.jid.2016.07.008","article-title":"Il-17 responses are the dominant inflammatory signal linking inverse, erythrodermic, and chronic plaque psoriasis","volume":"136","author":"Xing","year":"2016","journal-title":"J. Investig. Dermatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1084\/jem.20050500","article-title":"Plasmacytoid predendritic cells initiate psoriasis through interferon-alpha production","volume":"202","author":"Nestle","year":"2005","journal-title":"J. Exp. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.jaci.2016.08.056","article-title":"Il-1 and il-36 are dominant cytokines in generalized pustular psoriasis","volume":"140","author":"Johnston","year":"2017","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4733","DOI":"10.4049\/jimmunol.181.7.4733","article-title":"Induction of il-17+ t cell trafficking and development by ifn-gamma: Mechanism and pathological relevance in psoriasis","volume":"181","author":"Kryczek","year":"2008","journal-title":"J. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1038744","DOI":"10.3389\/fimmu.2022.1038744","article-title":"Applications of single-cell rna sequencing in atopic dermatitis and psoriasis","volume":"13","author":"Xia","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1111\/jdv.15340","article-title":"French guidelines on the use of systemic treatments for moderate-to-severe psoriasis in adults","volume":"33","author":"Amatore","year":"2019","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4881","DOI":"10.1073\/pnas.82.15.4881","article-title":"Inhibition of phosphoribosylaminoimidazolecarboxamide transformylase by methotrexate and dihydrofolic acid polyglutamates","volume":"82","author":"Allegra","year":"1985","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4","DOI":"10.12703\/P6-4","article-title":"Advances in treating psoriasis","volume":"6","author":"Belge","year":"2014","journal-title":"F1000Prime Rep."},{"key":"ref_26","first-page":"39","article-title":"Biologic treatments of psoriasis: An update for the clinician","volume":"15","author":"Brownstone","year":"2021","journal-title":"Biologics"},{"key":"ref_27","first-page":"ii14","article-title":"Psoriatic arthritis: Epidemiology, clinical features, course, and outcome","volume":"64","author":"Gladman","year":"2005","journal-title":"Ann. Rheum. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1111\/bjd.19229","article-title":"Dimethyl fumarate modulates the treg-th17 cell axis in patients with psoriasis","volume":"184","author":"Sulaimani","year":"2021","journal-title":"Br. J. Dermatol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2291","DOI":"10.1084\/jem.20100977","article-title":"Fumarates improve psoriasis and multiple sclerosis by inducing type ii dendritic cells","volume":"208","author":"Ghoreschi","year":"2011","journal-title":"J. Exp. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.tips.2017.11.002","article-title":"The pharmacokinetics of fumaric acid esters reveal their in vivo effects","volume":"39","author":"Mrowietz","year":"2018","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_31","first-page":"9613","article-title":"Real-world use of dimethyl fumarate in patients with plaque psoriasis: A delphi-based expert consensus","volume":"15","author":"Burlando","year":"2023","journal-title":"Dermatol. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"490","DOI":"10.4049\/jimmunol.1100123","article-title":"Mast cells and neutrophils release il-17 through extracellular trap formation in psoriasis","volume":"187","author":"Lin","year":"2011","journal-title":"J. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4930","DOI":"10.1182\/blood-2013-02-486217","article-title":"Mast cell and macrophage chemokines cxcl1\/cxcl2 control the early stage of neutrophil recruitment during tissue inflammation","volume":"121","author":"Dudeck","year":"2013","journal-title":"Blood"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Dunphy, S., and Gardiner, C.M. (2011). Nk cells and psoriasis. J. Biomed. Biotechnol., 2011.","DOI":"10.1155\/2011\/248317"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"941071","DOI":"10.3389\/fimmu.2022.941071","article-title":"Dendritic cells and macrophages in the pathogenesis of psoriasis","volume":"13","author":"Kamata","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1007\/BF00509233","article-title":"Involvement of complement in psoriasis and atopic dermatitis--measurement of c3a and c5a, c3, c4 and c1 inactivator","volume":"277","author":"Kapp","year":"1985","journal-title":"Arch. Dermatol. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1007\/s40257-018-0388-z","article-title":"Effect of age of onset of psoriasis on clinical outcomes with systemic treatment in the psoriasis longitudinal assessment and registry (psolar)","volume":"19","author":"Singh","year":"2018","journal-title":"Am. J. Clin. Dermatol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1002\/eji.200324174","article-title":"Monomethylfumarate affects polarization of monocyte-derived dendritic cells resulting in down-regulated th1 lymphocyte responses","volume":"34","author":"Litjens","year":"2004","journal-title":"Eur. J. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1111\/j.1523-1747.2003.12605.x","article-title":"Dimethylfumarate is a potent inducer of apoptosis in human t cells","volume":"121","author":"Treumer","year":"2003","journal-title":"J. Investig. Dermatol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.clim.2009.11.008","article-title":"Increased th17 cells are accompanied by foxp3(+) treg cell accumulation and correlated with psoriasis disease severity","volume":"135","author":"Zhang","year":"2010","journal-title":"Clin. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1159\/000093849","article-title":"Identification of lesional cd4+ cd25+ foxp3+ regulatory t cells in psoriasis","volume":"213","author":"Bovenschen","year":"2006","journal-title":"Dermatology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"397","DOI":"10.5021\/ad.2010.22.4.397","article-title":"Role of cd4cd25foxp3 regulatory t cells in psoriasis","volume":"22","author":"Yun","year":"2010","journal-title":"Ann. Dermatol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1111\/j.1365-2133.2010.09742.x","article-title":"Foxp3+ regulatory t cells and related cytokines differentially expressed in plaque vs. Guttate psoriasis vulgaris","volume":"163","author":"Yan","year":"2010","journal-title":"Br. J. Dermatol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1080\/09546634.2019.1605135","article-title":"Association of lymphopenia and eosinophilia with dimethylfumarate treatment efficacy and tolerability in psoriasis: A retrospective study","volume":"31","author":"Bovenschen","year":"2020","journal-title":"J. Dermatol. Treat."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1111\/j.1365-2133.2009.09267.x","article-title":"Treatment of severe, recalcitrant, chronic plaque psoriasis with fumaric acid esters: A prospective study","volume":"162","author":"Wain","year":"2010","journal-title":"Br. J. Dermatol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1159\/000017903","article-title":"Fumaric acid esters suppress peripheral cd4- and cd8-positive lymphocytes in psoriasis","volume":"196","author":"Hoxtermann","year":"1998","journal-title":"Dermatology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1111\/j.1365-2133.2005.06728.x","article-title":"Fumaric acid esters for severe psoriasis: A retrospective review of 58 cases","volume":"153","author":"Harries","year":"2005","journal-title":"Br. J. Dermatol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/21\/6820\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:13:34Z","timestamp":1760130814000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/21\/6820"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,28]]},"references-count":47,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2023,11]]}},"alternative-id":["jcm12216820"],"URL":"https:\/\/doi.org\/10.3390\/jcm12216820","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,28]]}}}