{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T22:12:11Z","timestamp":1790892731837,"version":"4.1.0"},"reference-count":120,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2019,2,10]],"date-time":"2019-02-10T00:00:00Z","timestamp":1549756800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006595","name":"Unitatea Executiva pentru Finantarea Invatamantului Superior, a Cercetarii, Dezvoltarii si Inovarii","doi-asserted-by":"publisher","award":["PN-III-P1-1.2-PCCDI-2017-0341"],"award-info":[{"award-number":["PN-III-P1-1.2-PCCDI-2017-0341"]}],"id":[{"id":"10.13039\/501100006595","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006595","name":"Unitatea Executiva pentru Finantarea Invatamantului Superior, a Cercetarii, Dezvoltarii si Inovarii","doi-asserted-by":"publisher","award":["PN.19.29.01.01\/2019"],"award-info":[{"award-number":["PN.19.29.01.01\/2019"]}],"id":[{"id":"10.13039\/501100006595","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministerul Educa\u021biei \u0219i Cercet\u0103rii \u0218tiin\u021bifice","award":["7PFE\/16.10.2018"],"award-info":[{"award-number":["7PFE\/16.10.2018"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Psoriasis vulgaris is a chronic, immune-mediated, inflammatory, polygenic skin disorder affecting approximately 2% of the population. It has a great impact on quality of life; patients often experience depression, anxiety, stigma as well as suicidal behavior. Even though psoriasis is one of the most studied dermatological conditions, the pathogenesis of the disease is still not completely elucidated. The complex interactions between keratinocytes, dendritic cells, T-lymphocytes, neutrophils and mast cells are responsible for the histopathological changes seen in psoriasis. The pathogenic model leading to the formation of psoriatic plaques has however evolved a lot over the years. There is now enough evidence to support the role of interleukin (IL) -23, IL-17, IL-22, T helper (Th) -17 cells, Th-22 cells, T regulatory cells, transforming growth factor (TGF)-\u03b21 and IL-10 in the pathogenesis of the disease. Moreover, several inflammatory and anti-inflammatory molecules are currently being investigated, some of them showing promising results. The aim of this paper is to look over the most recent advances in the immunological pathways involved in the pathogenesis of psoriasis vulgaris.<\/jats:p>","DOI":"10.3390\/ijms20030739","type":"journal-article","created":{"date-parts":[[2019,2,12]],"date-time":"2019-02-12T03:18:20Z","timestamp":1549941500000},"page":"739","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":133,"title":["Advances in Understanding the Immunological Pathways in Psoriasis"],"prefix":"10.3390","volume":"20","author":[{"given":"Simona-Roxana","family":"Georgescu","sequence":"first","affiliation":[{"name":"Department of Dermatology, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania"},{"name":"Department of Dermatology, Victor Babes Hospital of Infectious Diseases, 030303 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mircea","family":"Tampa","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania"},{"name":"Department of Dermatology, Victor Babes Hospital of Infectious Diseases, 030303 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4530-7965","authenticated-orcid":false,"given":"Constantin","family":"Caruntu","sequence":"additional","affiliation":[{"name":"Department of Physiology, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania"},{"name":"Department of Dermatology, Prof. N.C. Paulescu National Institute of Diabetes, Nutrition and Metabolic Diseases, 030167 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2461-1151","authenticated-orcid":false,"given":"Maria-Isabela","family":"Sarbu","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina-Iulia","family":"Mitran","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madalina-Irina","family":"Mitran","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Matei","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Constantin","sequence":"additional","affiliation":[{"name":"Department of Immunology, Victor Babes National Institute of Pathology, 050096 Bucharest, Romania"},{"name":"Department of Pathology, Colentina University Hospital, 020125 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Neagu","sequence":"additional","affiliation":[{"name":"Department of Immunology, Victor Babes National Institute of Pathology, 050096 Bucharest, Romania"},{"name":"Department of Pathology, Colentina University Hospital, 020125 Bucharest, Romania"},{"name":"Faculty of Biology, University of Bucharest, 030018 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,2,10]]},"reference":[{"key":"ref_1","unstructured":"Goldsmith, L.A., and Katz, S.I. (2012). Psoriasis. Fitzpatrick\u2019s Dermatology in General Medicine, McGrawHill. [8th ed.]."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Burns, T., and Breathnach, S. (2010). Psoriasis. Rook\u2019s Textbook of Dermatology, Wiley Blackwell. [8th ed.].","DOI":"10.1002\/9781444317633"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Burgdorf, W.H.C., and Plewig, G. (2009). Psoriasis. Braun-Falco\u2019s Dermatology, Springer. [3rd ed.].","DOI":"10.1007\/978-3-540-29316-3"},{"key":"ref_4","unstructured":"Bolognia, J.L., and Jorizzo, J.L. (2012). Psoriasis. Dermatology, Elsevier. [3rd ed.]."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"186","DOI":"10.22543\/7674.42.P186192","article-title":"Therapeutic challenges in a case of psoriasis with nail onset","volume":"4","author":"Mitran","year":"2017","journal-title":"J. Mind Med. Sci."},{"key":"ref_6","first-page":"75","article-title":"Biological therapies in psoriasis-revisited","volume":"56","author":"Georgescu","year":"2018","journal-title":"Rom. J. Intern. Med."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Tampa, M., Sarbu, M.I., Mitran, M.I., Mitran, C.I., Matei, C., and Georgescu, S.R. (2018). The Pathophysiological Mechanisms and the Quest for Biomarkers in Psoriasis, a Stress-Related Skin Disease. Dis. Markers, 2018.","DOI":"10.1155\/2018\/5823684"},{"key":"ref_8","first-page":"19","article-title":"Sexual dysfunctions in psoriatic patients","volume":"1","author":"Sarbu","year":"2014","journal-title":"J. Mind Med. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"43","DOI":"10.37358\/RC.17.1.5385","article-title":"Vitamin C and thiobarbituric acid reactive substances (TBARS) in psoriasis vulgaris related to psoriasis area severity index (PASI)","volume":"68","author":"Tampa","year":"2017","journal-title":"Rev. Chim."},{"key":"ref_10","unstructured":"Mobini, N., Toussaint, S., and Kamino, H. (2005). Noninfectious Erythematous, Papular, and Squamous Diseases. Lever\u2019s Histopathology of the Skin, Lippincott Williams & Wilkins."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4","DOI":"10.22543\/7674.41.P0412","article-title":"Adverse reactions of biological therapies in patients with psoriasis","volume":"4","author":"Tampa","year":"2017","journal-title":"J. Mind Med Sci."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Chiricozzi, A., Romanelli, P., Volpe, E., Borsellino, G., and Romanelli, M. (2018). Scanning the Immunopathogenesis of Psoriasis. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19010179"},{"key":"ref_13","first-page":"962","article-title":"Infliximab Biosimilar Versus Methotrexate for the Treatment of Moderate to Severe Psoriasis","volume":"65","author":"Sarbu","year":"2017","journal-title":"Farmacia"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"513","DOI":"10.2217\/bmm.14.76","article-title":"Proteomics focusing on immune markers in psoriatic arthritis","volume":"9","author":"Caruntu","year":"2015","journal-title":"Biomark. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5621","DOI":"10.1038\/ncomms6621","article-title":"The antimicrobial peptide LL37 is a T-cell autoantigen in psoriasis","volume":"5","author":"Lande","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2186","DOI":"10.1084\/jem.21213insight3","article-title":"An autoimmune \u201cattack\u201d on melanocytes triggers psoriasis and cellular hyperplasia","volume":"212","author":"Krueger","year":"2015","journal-title":"J. Exp. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1038\/nature06116","article-title":"Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide","volume":"449","author":"Lande","year":"2007","journal-title":"Nature"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1038\/jid.2011.259","article-title":"Cathelicidin antimicrobial peptide LL-37 in psoriasis enables keratinocyte reactivity against TLR9 ligands","volume":"132","author":"Morizane","year":"2012","journal-title":"J. Investig. Dermatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3","DOI":"10.2174\/2468422807666180320125713","article-title":"Biomarkers Insights in Psoriasis-Regulatory Cytokines","volume":"7","author":"Surcel","year":"2018","journal-title":"Curr. Biomark."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1038\/nbt.1903","article-title":"Therapeutic targeting of the IL-12\/23 pathways: Generation and characterization of ustekinumab","volume":"29","author":"Benson","year":"2011","journal-title":"Nat. Biotechnol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Georgescu, S.R., S\u00e2rbu, M.I., Matei, C., Ilie, M.A., Caruntu, C., Constantin, C., Neagu, M., and Tampa, M. (2017). Capsaicin: Friend or foe in skin cancer and other related malignancies?. Nutrients, 9.","DOI":"10.3390\/nu9121365"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1051\/medsci\/20163203009","article-title":"Immunopathologie du psoriasis-From bench to bedside","volume":"32","author":"Bouaziz","year":"2016","journal-title":"Med. Sci. (Paris)"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/s00281-015-0539-8","article-title":"Update on psoriasis immunopathogenesis and targeted immunotherapy","volume":"38","author":"Mahil","year":"2016","journal-title":"Semin. Immunopathol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1111\/1523-1747.ep12477880","article-title":"Increased IL-6 production by monocytes and keratinocytes in patients with psoriasis","volume":"97","author":"Neuner","year":"1991","journal-title":"J. Investig. Dermatol."},{"key":"ref_25","first-page":"1","article-title":"Targeting IL-23 in psoriasis: Current perspectives","volume":"8","author":"Fotiadou","year":"2018","journal-title":"Psoriasis (Auckl)"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1616","DOI":"10.1111\/jdv.14433","article-title":"The role of IL-23 and the IL-23\/TH 17 immune axis in the pathogenesis and treatment of psoriasis","volume":"31","author":"Girolomoni","year":"2017","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5","DOI":"10.12688\/f1000research.7927.1","article-title":"Recent advances in understanding psoriasis","volume":"5","author":"Eberle","year":"2016","journal-title":"F1000 Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1084\/jem.20030451","article-title":"Increased expression of interleukin 23 p19 and p40 in lesional skin of patients with psoriasis vulgaris","volume":"199","author":"Lee","year":"2004","journal-title":"J. Exp. Med."},{"key":"ref_29","first-page":"148","article-title":"Translational Mini-Review Series on Th17 Cells: Development of mouse and human T helper 17 cells","volume":"159","author":"Suddason","year":"2010","journal-title":"Clin. Exp. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1177\/2040622318759282","article-title":"Interleukin 23 in the skin: Role in psoriasis pathogenesis and selective interleukin 23 blockade as treatment","volume":"9","author":"Chan","year":"2018","journal-title":"Ther. Adv. Chronic Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"43310","DOI":"10.1038\/srep43310","article-title":"CCN1 promotes IL-1\u03b2 production in keratinocytes by activating p38 MAPK signaling in psoriasis","volume":"7","author":"Sun","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Zwicker, S., Hattinger, E., Bureik, D., Batycka-Baran, A., Schmidt, A., Gerber, P.A., Rothenfusser, S., Gilliet, M., Ruzicka, T., and Wolf, R. (2017). Th17 micro-milieu regulates NLRP1-dependent caspase-5 activity in skin autoinflammation. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0175153"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"a028522","DOI":"10.1101\/cshperspect.a028522","article-title":"Interleukin 17 family cytokines: Signaling mechanisms, biological activities, and therapeutic implications","volume":"10","author":"Monin","year":"2018","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e000284","DOI":"10.1136\/rmdopen-2016-000284","article-title":"Update on interleukin-17: A role in the pathogenesis of inflammatory arthritis and implication for clinical practice","volume":"3","author":"Miossec","year":"2017","journal-title":"RMD Open"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1643","DOI":"10.2147\/DDDT.S92128","article-title":"Spotlight on ixekizumab for the treatment of moderate-to-severe plaque psoriasis: Design, development, and use in therapy","volume":"11","author":"Giunta","year":"2017","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1111\/all.13051","article-title":"Immunopathology alters Th17 cell glucocorticoid sensitivity","volume":"72","author":"Banuelos","year":"2017","journal-title":"Allergy"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Diani, M., Altomare, G., and Reali, E. (2016). T helper cell subsets in clinical manifestations of psoriasis. J. Immunol. Res.","DOI":"10.1155\/2016\/7692024"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1155\/MI.2005.273","article-title":"Serum levels of TNF-\u03b1, IFN-\u03b3, IL-6, IL-8, IL-12, IL-17, and IL-18 in patients with active psoriasis and correlation with disease severity","volume":"2005","author":"Arican","year":"2005","journal-title":"Mediat. Inflamm."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1046\/j.1523-1747.1998.00347.x","article-title":"Interleukin-17 and interferon-\u03b3 synergize in the enhancement of proinflammatory cytokine production by human keratinocytes","volume":"111","author":"Teunissen","year":"1998","journal-title":"J. Investig. Dermatol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.jaci.2012.04.024","article-title":"IL-17A is essential for cell activation and inflammatory gene circuits in subjects with psoriasis","volume":"130","author":"Krueger","year":"2012","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1080\/14712598.2018.1481503","article-title":"Secukinumab in moderate-to-severe plaque psoriasis: A multi-center, retrospective, real-life study up to 52 weeks observation","volume":"18","author":"Galluzzo","year":"2018","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1970","DOI":"10.1016\/j.jid.2016.06.009","article-title":"Keratinocyte-derived IL-17E contributes to inflammation in psoriasis","volume":"136","author":"Senra","year":"2016","journal-title":"J. Investig. Dermatol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1002\/eji.201546070","article-title":"AhR modulates the IL-22-producing cell proliferation\/recruitment in imiquimod-induced psoriasis mouse model","volume":"46","author":"Cochez","year":"2016","journal-title":"Eur. J. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.jaci.2015.01.033","article-title":"Human mast cells are major IL-22 producers in patients with psoriasis and atopic dermatitis","volume":"136","author":"Mashiko","year":"2015","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1016\/j.autrev.2013.11.008","article-title":"Interleukin-22: A likely target for treatment of autoimmune diseases","volume":"13","author":"Yang","year":"2014","journal-title":"Autoimmun. Rev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e2344","DOI":"10.1038\/cddis.2016.201","article-title":"Luteolin-7-glucoside inhibits IL-22\/STAT3 pathway, reducing proliferation, acanthosis, and inflammation in keratinocytes and in mouse psoriatic model","volume":"7","author":"Palombo","year":"2016","journal-title":"Cell Death Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1038\/ni.3504","article-title":"CD69 controls the uptake of L-tryptophan through LAT1-CD98 and AhR-dependent secretion of IL-22 in psoriasis","volume":"17","author":"Cibrian","year":"2016","journal-title":"Nat. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/S0065-2776(07)96002-2","article-title":"Regulation of interferon-\u03b3 during innate and adaptive immune responses","volume":"96","author":"Schoenborn","year":"2007","journal-title":"Adv. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1189\/jlb.0603252","article-title":"Interferon-\u03b3: An overview of signals, mechanisms and functions","volume":"75","author":"Schroder","year":"2004","journal-title":"J. Leukoc. Biol."},{"key":"ref_50","first-page":"S9-18","article-title":"The interferon receptors","volume":"24","author":"Pestka","year":"1997","journal-title":"Semin. Oncol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1038\/jid.2012.426","article-title":"CD8 T cells and IFN-\u03b3 emerge as critical players for psoriasis in a novel model of mouse psoriasiform skin inflammation","volume":"133","author":"Duarte","year":"2013","journal-title":"J. Investig. Dermatol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1046\/j.1523-1747.1999.00749.x","article-title":"The majority of epidermal T cells in psoriasis vulgaris lesions can produce type 1 cytokines, interferon-\u03b3, interleukin-2, and tumor necrosis factor-\u03b1, defining TC1 (Cytotoxic T Lymphocyte) and TH1 effector populations: 1 a type 1 differentiation bias is also measured in circulating blood T cells in psoriatic patients","volume":"113","author":"Austin","year":"1999","journal-title":"J. Investig. Dermatol."},{"key":"ref_53","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-\u03b3: Mechanism and pathological relevance in psoriasis","volume":"181","author":"Kryczek","year":"2008","journal-title":"J. Immunol."},{"key":"ref_54","first-page":"163","article-title":"Serum interferon-gamma is a psoriasis severity and prognostic marker","volume":"84","author":"Abdallah","year":"2009","journal-title":"Cutis"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/j.jaci.2014.05.046","article-title":"Humanized anti\u2013IFN-\u03b3 (HuZAF) in the treatment of psoriasis","volume":"135","author":"Harden","year":"2015","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1590\/abd1806-4841.20186123","article-title":"The potential role of Th17 lymphocytes in patients with psoriasis","volume":"93","author":"Mansouri","year":"2018","journal-title":"An. Bras. Dermatol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Boutet, M.A., Nerviani, A., Gallo Afflitto, G., and Pitzalis, C. (2018). Role of the IL-23\/IL-17 axis in psoriasis and psoriatic arthritis: The clinical importance of its divergence in skin and joints. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19020530"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1038\/nri3707","article-title":"The IL-23-IL-17 immune axis: From mechanisms to therapeutic testing","volume":"14","author":"Gaffen","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1016\/j.immuni.2015.12.003","article-title":"Th17 cell pathway in human immunity: Lessons from genetics and therapeutic interventions","volume":"43","author":"Patel","year":"2015","journal-title":"Immunity"},{"key":"ref_60","first-page":"3573","article-title":"Th22 cells represent a distinct human T cell subset involved in epidermal immunity and remodeling","volume":"119","author":"Eyerich","year":"2009","journal-title":"J. Clin. Investig."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1155\/2013\/856056","article-title":"Serum levels of selected Th17 and Th22 cytokines in psoriatic patients","volume":"35","author":"Kowal","year":"2013","journal-title":"Dis. Markers"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.cellimm.2014.06.007","article-title":"An increased proportion of circulating Th22 and Tc22 cells in psoriasis","volume":"290","author":"Luan","year":"2014","journal-title":"Cell. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"R136","DOI":"10.1186\/ar4317","article-title":"Th17 and Th22 cells in psoriatic arthritis and psoriasis","volume":"15","author":"Benham","year":"2013","journal-title":"Arthritis Res. Ther."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3111","DOI":"10.4049\/jimmunol.1302313","article-title":"Epidermal Th22 and Tc17 cells form a localized disease memory in clinically healed psoriasis","volume":"192","author":"Cheuk","year":"2014","journal-title":"J. Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1097\/00054725-199911000-00009","article-title":"Th1\/Th2 cells","volume":"5","author":"Romagnani","year":"1999","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1111\/bjd.12631","article-title":"Bimodal immune activation in psoriasis","volume":"170","author":"Christophers","year":"2014","journal-title":"Br. J. Dermatol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"37977","DOI":"10.1038\/srep37977","article-title":"Pharmacologic modulation of ROR\u03b3t translates to efficacy in preclinical and translational models of psoriasis and inflammatory arthritis","volume":"6","author":"Xue","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1080\/13543776.2017.1236918","article-title":"ROR\u03b3 antagonists and inverse agonists: A patent review","volume":"27","author":"Bronner","year":"2017","journal-title":"Expert Opin. Ther. Pat."},{"key":"ref_69","first-page":"17","article-title":"The role of regulatory T cells and anti-inflammatory cytokines in psoriasis","volume":"27","author":"Placek","year":"2018","journal-title":"Acta Dermatovenerol. Alp. Panonica Adriat."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"405","DOI":"10.5114\/ada.2017.71105","article-title":"The role of regulatory T cells and genes involved in their differentiation in pathogenesis of selected inflammatory and neoplastic skin diseases. Part II: The Treg role in skin diseases pathogenesis","volume":"34","author":"Nedoszytko","year":"2017","journal-title":"Adv. Dermatol. Allergol.\/Post\u0229p. Dermatol. Alergol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"517","DOI":"10.5114\/pdia.2017.67053","article-title":"The role of regulatory T cells and genes involved in their differentiation in pathogenesis of selected inflammatory and neoplastic skin diseases. Part III: Polymorphisms of genes involved in Tregs\u2019 activation and function","volume":"34","author":"Nedoszytko","year":"2017","journal-title":"Postepy Dermatol. Alergol."},{"key":"ref_72","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_73","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_74","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1111\/j.1365-2133.2008.08504.x","article-title":"Profiles of Foxp3+ regulatory T cells in eczematous dermatitis, psoriasis vulgaris and mycosis fungoides","volume":"158","author":"Fujimura","year":"2008","journal-title":"Br. J. Dermatol."},{"key":"ref_75","first-page":"25","article-title":"T regulatory CD4+ CD25high lymphocytes in peripheral blood of patients suffering from psoriasis","volume":"27","author":"Pawlaczyk","year":"2010","journal-title":"Postepy Dermatol. Alergol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.clim.2013.06.007","article-title":"Psoriasis patients exhibit impairment of the high potency CCR5(+) T regulatory cell subset","volume":"149","author":"Soler","year":"2013","journal-title":"Clin. Immunol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1038\/jid.2011.139","article-title":"Foxp3+ regulatory T cells of psoriasis patients easily differentiate into IL-17A-producing cells and are found in lesional skin","volume":"131","author":"Bovenschen","year":"2011","journal-title":"J. Investig. Dermatol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1111\/exd.13249","article-title":"Roles of microRNAs in psoriasis: Immunological functions and potential biomarkers","volume":"26","author":"Liu","year":"2017","journal-title":"Exp. Dermatol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2551","DOI":"10.1172\/JCI97426","article-title":"MicroRNA-210 overexpression promotes psoriasis-like inflammation by inducing Th1 and Th17 cell differentiation","volume":"128","author":"Wu","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.clim.2013.10.009","article-title":"Up-regulation of microRNA-210 induces immune dysfunction via targeting FOXP3 in CD4(+) T cells of psoriasis vulgaris","volume":"150","author":"Zhao","year":"2014","journal-title":"Clin. Immunol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"9","DOI":"10.31768\/2312-8852.2016.38(1):9-12","article-title":"HIF-1--a big chapter in the cancer tale","volume":"38","year":"2016","journal-title":"Exp. Oncol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1038\/jid.2009.252","article-title":"A role for TGFbeta signaling in the pathogenesis of psoriasis","volume":"130","author":"Han","year":"2010","journal-title":"J. Investig. Dermatol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1002\/jcla.21717","article-title":"Serum vascular endothelial growth factor, transforming growth factor \u03b21, and nitric oxide levels in patients with psoriasis vulgaris: Their correlation to disease severity","volume":"28","author":"Meki","year":"2014","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_84","first-page":"2","article-title":"Serum concentrations of transforming growth factor beta 1 in patients with psoriasis vulgaris","volume":"12","author":"Nockowski","year":"2004","journal-title":"Acta Dermatovenerol. Croat."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1111\/1440-1681.12294","article-title":"Transforming growth factor-\u03b21 mediates psoriasis-like lesions via a Smad3-dependent mechanism in mice","volume":"41","author":"Zhang","year":"2014","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/jid.2012.411","article-title":"TGF\u03b21, an epidermal controller of skin dendritic cell homeostasis","volume":"133","author":"Kitoh","year":"2013","journal-title":"J. Investig. Dermatol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.cyto.2014.10.031","article-title":"Interleukin-10 paradox: A potent immunoregulatory cytokine that has been difficult to harness for immunotherapy","volume":"74","author":"Saxena","year":"2015","journal-title":"Cytokine"},{"key":"ref_88","first-page":"36","article-title":"Pathologic patterns of interleukin 10 expressiona review","volume":"25","author":"Miller","year":"2015","journal-title":"Biochem. Med. (Zagreb)"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.7314\/APJCP.2015.16.3.1247","article-title":"Novel mutations in IL-10 promoter region -377 (C>T), -150 (C>A) and their association with psoriasis in the saudi population","volume":"16","author":"Halwani","year":"2015","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_90","first-page":"317","article-title":"Serum levels of IL-10 and IL-22 cytokines in patients with psoriasis","volume":"13","author":"Sobhan","year":"2016","journal-title":"Iran. J. Immunol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.cyto.2014.01.008","article-title":"Polymorphisms in the TNF-\u03b1 and IL-10 gene promoters and risk of psoriasis and correlation with disease severity","volume":"66","author":"Karam","year":"2014","journal-title":"Cytokine"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.clim.2017.04.010","article-title":"IL-10 producing Bregs are impaired in psoriatic arthritis and psoriasis and inversely correlate with IL-17- and IFN\u03b3-producing T cells","volume":"184","author":"Mavropoulos","year":"2017","journal-title":"Clin. Immunol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"3809","DOI":"10.4049\/jimmunol.1602142","article-title":"Cutting edge: Selective oral ROCK2 inhibitor reduces clinical scores in patients with psoriasis vulgaris and normalizes skin pathology via concurrent regulation of IL-17 and IL-10","volume":"198","author":"Weiss","year":"2017","journal-title":"J. Immunol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.imlet.2014.11.008","article-title":"Exopolysaccharides from Cyanobacterium aponinum from the Blue Lagoon in Iceland increase IL-10 secretion by human dendritic cells and their ability to reduce the IL-17+ROR\u03b3t+\/IL-10+FoxP3+ ratio in CD4+ T cells","volume":"163","author":"Gudmundsdottir","year":"2015","journal-title":"Immunol. Lett."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.jid.2016.09.035","article-title":"ACKR2: Nature\u2019s Decoy Receptor Lures Unsuspecting Chemokines in Psoriasis","volume":"137","author":"Mabuchi","year":"2017","journal-title":"J. Investig. Dermatol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1016\/j.ajpath.2012.06.042","article-title":"Elevated expression of the chemokine-scavenging receptor D6 is associated with impaired lesion development in psoriasis","volume":"181","author":"Singh","year":"2012","journal-title":"Am. J. Pathol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"3003","DOI":"10.1074\/jbc.M117.809780","article-title":"MicroRNA-146 and cell trauma down-regulate expression of the psoriasis-associated atypical chemokine receptor ACKR2","volume":"293","author":"Shams","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.jid.2016.07.039","article-title":"Spread of psoriasiform inflammation to remote tissues is restricted by the atypical chemokine receptor ACKR2","volume":"137","author":"Shams","year":"2017","journal-title":"J. Investig. Dermatol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"e5374","DOI":"10.1590\/1414-431x20165374","article-title":"CD19+ B cell subsets in the peripheral blood and skin lesions of psoriasis patients and their correlations with disease severity","volume":"49","author":"Lu","year":"2016","journal-title":"Braz. J. Med. Biol. Res."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1189\/jlb.1112562","article-title":"Regulatory B cells suppress imiquimod-induced, psoriasis-like skin inflammation","volume":"94","author":"Yanaba","year":"2013","journal-title":"J. Leukoc. Biol."},{"key":"ref_101","first-page":"148","article-title":"A new kid on the block: IL-10+ regulatory B cells and a possible role in psoriasis","volume":"14","author":"Darabi","year":"2009","journal-title":"J. Pediatr. Pharmacol. Ther."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1111\/jdv.15101","article-title":"Is the humoral immunity dispensable for the pathogenesis of psoriasis?","volume":"33","author":"Thomas","year":"2019","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1830","DOI":"10.1016\/j.jaci.2015.09.055","article-title":"The tryptophan metabolism enzyme L-kynureninase is a novel inflammatory factor in psoriasis and other inflammatory diseases","volume":"137","author":"Harden","year":"2016","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"96101","DOI":"10.1172\/jci.insight.96101","article-title":"A type of human skin dendritic cell marked by CD5 is associated with the development of inflammatory skin disease","volume":"2","author":"Korenfeld","year":"2017","journal-title":"JCI Insight"},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Buerger, C., Shirsath, N., Lang, V., Berard, A., Diehl, S., Kaufmann, R., Boehncke, W.H., and Wolf, P. (2017). Inflammation dependent mTORC1 signaling interferes with the switch from keratinocyte proliferation to differentiation. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0180853"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"74236","DOI":"10.18632\/oncotarget.12371","article-title":"Overexpression and potential roles of NRIP1 in psoriasis","volume":"7","author":"Luan","year":"2016","journal-title":"Oncotarget"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"92979","DOI":"10.1172\/jci.insight.92979","article-title":"Tristetraprolin expression by keratinocytes controls local and systemic inflammation","volume":"2","author":"Andrianne","year":"2017","journal-title":"JCI Insight"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1038\/s41598-017-01411-1","article-title":"Immune-checkpoint protein VISTA critically regulates the IL-23\/IL-17 inflammatory axis","volume":"7","author":"Li","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_109","first-page":"1030","article-title":"Phenotypic changes of lymphocyte populations in psoriasiform dermatitis animal model","volume":"17","author":"Surcel","year":"2019","journal-title":"Exp. Ther. Med."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"15395","DOI":"10.1038\/ncomms15395","article-title":"TWEAK mediates inflammation in experimental atopic dermatitis and psoriasis","volume":"8","author":"Sidler","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"38825","DOI":"10.1038\/srep38825","article-title":"Overexpression of Glucocorticoid-induced Leucine Zipper (GILZ) increases susceptibility to Imiquimod-induced psoriasis and involves cutaneous activation of TGF-\u03b21","volume":"6","author":"Carceller","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.ebiom.2016.10.022","article-title":"Prokineticin 2 plays a pivotal role in psoriasis","volume":"13","author":"He","year":"2016","journal-title":"EBioMedicine"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"34690","DOI":"10.1038\/srep34690","article-title":"Upregulation of ANGPTL6 in mouse keratinocytes enhances susceptibility to psoriasis","volume":"6","author":"Tanigawa","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/j.jid.2015.12.011","article-title":"Human \u00df-Defensin 3 and Its Mouse Ortholog Murine \u00df-Defensin 14 Activate Langerhans Cells and Exacerbate Psoriasis-Like Skin Inflammation in Mice","volume":"136","author":"Sweeney","year":"2016","journal-title":"J. Investig. Dermatol."},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Dou, R., Liu, Z., Yuan, X., Xiangfei, D., Bai, R., Bi, Z., Yang, P., Yang, Y., Dong, Y., and Su, W. (2017). PAMs ameliorates the imiquimod-induced psoriasis-like skin disease in mice by inhibition of translocation of NF-\u03baB and production of inflammatory cytokines. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0176823"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"21132","DOI":"10.1038\/srep21132","article-title":"Heme oxygenase-1 induction attenuates imiquimod-induced psoriasiform inflammation by negative regulation of Stat3 signaling","volume":"6","author":"Zhang","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.intimp.2015.12.035","article-title":"Astilbin inhibits Th17 cell differentiation and ameliorates imiquimod-induced psoriasis-like skin lesions in BALB\/c mice via Jak3\/Stat3 signaling pathway","volume":"32","author":"Di","year":"2016","journal-title":"Int. Immunopharmacol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.ejphar.2015.12.040","article-title":"Paeoniflorin inhibits imiquimod-induced psoriasis in mice by regulating Th17 cell response and cytokine secretion","volume":"772","author":"Zhao","year":"2016","journal-title":"Eur. J. Pharmacol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.3892\/ijmm.2017.2930","article-title":"Paeonol ameliorates imiquimod-induced psoriasis-like skin lesions in BALB\/c mice by inhibiting the maturation and activation of dendritic cells","volume":"39","author":"Meng","year":"2017","journal-title":"Int. J. Mol. Med."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1089\/ars.2015.6368","article-title":"Effects of human mesenchymal stem cells transduced with superoxide dismutase on imiquimod-induced psoriasis-like skin inflammation in mice","volume":"24","author":"Sah","year":"2016","journal-title":"Antioxid. Redox Signal."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/3\/739\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:30:57Z","timestamp":1760185857000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/3\/739"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,10]]},"references-count":120,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2019,2]]}},"alternative-id":["ijms20030739"],"URL":"https:\/\/doi.org\/10.3390\/ijms20030739","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,2,10]]}}}