title: TNF-α inhibitors reduce the pathological Th1-Th17/Th2imbalance in cutaneous mesenchymal stem cells of psoriasis patients.
abstract: Psoriasis is a disease characterized by an imbalance between Th1and Th17and Th2inflammatory axes, in which cutaneous mesenchymal stem cells (MSCs) are early involved, as they show a greater relative expression of several genes encoding for Th1and Th17cytokines. Therapeutic implications of TNF-α inhibitors on differentiated skin cells have been largely described in psoriasis; however, their effects on MSCs derived from patients with psoriasis have been only partially described. The aim of this work was to evaluate the effect of TNF-α inhibitors on cytokine milieu expressed by MSCs isolated from the skin of patients with psoriasis. Resident MSCs from skin of patients with psoriasis and healthy subjects have been isolated, characterized and profiled by PCR and ELISA for the expression of 22 cytokines involved in Th1, Th2and Th17pathways, both before and after 12 weeks therapy with TNF-α inhibitors. The administration of TNF-α inhibitors for 12-weeks acts on MSCs as follows: it reduces the expression of several Th1-Th17cytokines whose levels are elevated at baseline (IL-6, IL-8, IL-12, IL-23A, IFN-γ, TNF-α, CCL2, CCL20, CXCL2, CXCL5, IL-17A, IL-17C, IL-17F, IL-21, G-CSF). Similarly, it enhances the expression of several Th2cytokines which are underexpressed at baseline (IL-2, IL-4, IL-5), reducing the expression of those overexpressed at baseline (TGF-β and IL-13). TNF-α inhibitors could contribute to reduce the pathological imbalance between the Th1-Th17vs Th2axis in MSCs of patients with psoriasis.
authors.affiliation: Dermatological Clinic, Department of Molecular and Clinical Sciences, Marche Polytechnic University, Ancona, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Campanati
authors.affiliation: Department of Molecular and Clinical Sciences - Histology, Marche Polytechnic University, Ancona, Italy.
authors.forename: Monia
authors.initials: M
authors.lastname: Orciani
authors.affiliation: Department of Molecular and Clinical Sciences - Histology, Marche Polytechnic University, Ancona, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Lazzarini
authors.affiliation: Dermatological Clinic, Department of Molecular and Clinical Sciences, Marche Polytechnic University, Ancona, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Ganzetti
authors.affiliation: Dermatological Clinic, Department of Molecular and Clinical Sciences, Marche Polytechnic University, Ancona, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Consales
authors.affiliation: Department of Molecular and Clinical Sciences - Histology, Marche Polytechnic University, Ancona, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Sorgentoni
authors.affiliation: Department of Molecular and Clinical Sciences - Histology, Marche Polytechnic University, Ancona, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Di Primio
authors.affiliation: Dermatological Clinic, Department of Molecular and Clinical Sciences, Marche Polytechnic University, Ancona, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Offidani
mesh_terms: D000068879:Adalimumab / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D016022:Case-Control Studies; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D000068800:Etanercept / Q000627:therapeutic use; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D016130:Immunophenotyping; D059630:Mesenchymal Stem Cells / Q000276:immunology / Q000378:metabolism*; D011446:Prospective Studies; D011565:Psoriasis / Q000188:drug therapy* / Q000503:physiopathology*; D012333:RNA, Messenger / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000068879:Adalimumab; D000068800:Etanercept
keywords: 
  ELISA
  ; PCR array; Th1-Th2-Th17 imbalances; mesenchymal stem cells; psoriasis