Abstract
The expression of genes encoding for Th1, Th2 and Th17 cytokines has been extensively evaluated in differentiated skin cells of psoriatic patients. The microenvironment exerts a control on the phenotype of resident mesenchymal stem cells (MSCs) into the skin of psoriasis patients. Aim of the study was to extensively evaluate the relative expression of 43 genes encoding for Th1, Th2 and Th17 cytokines in MSCs isolated from skin of psoriasis patients. MSCs resident into psoriatic skin were isolated, characterized and profiled by PCR array for the relative expression of genes encoding for cytokines involved in Th1, Th2 and Th17 pathways. MSCs isolated from the skin of healthy subjects were used as control. The MSCs isolated from skin of psoriasis patients showed a greater relative expression of the most part of the analyzed genes encoding for Th1 and Th17 cytokines: INF-γ, CCR5, CXCL9, CXCL10, IL6, IL8, TNF-α, IL23A, CCL2, CCL20, CXCL2, CXCL5, IL17C, IL17F, IL17RA, IL21, TLR2 than healthy subjects. On the contrary, the relative expression of genes encoding for Th2 cytokines: CCL1, CCL22, CXCL12, IL2, IL3, IL4, IL13B, IL 22, IL 27, TGF-β1, was similar between the MSCs isolated from psoriasis and healthy subjects. In conclusion, the MSCs isolated from psoriasis show an imbalance between the Th1-Th17 and Th2 pathways, which reflects the well-known abnormal balance observed in differentiated skin cells. This evidence could strengthen the hypothesis of an early involvement of resident MSCs in the pathogenesis of psoriasis.
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References
Atzeni F, Ventura D, Batticciotto A, Boccassini L, Sarzi-Puttini P (2012) Interleukin 6 blockade: tocilizumab in psoriatic arthritis. J Rheumatol Suppl 89:97–99
Campanati A, Giuliodori K, Ganzetti G, Liberati G, Offidani AM (2010) A patient with psoriasis and vitiligo treated with etanercept. Am J Clin Dermatol 11(Suppl 1):46–48
Campanati A, Orciani M, Gorbi S, Regoli F, Di Primio R, Offidani A (2012) Effect of biologic therapies targeting tumour necrosis factor-α on cutaneous mesenchymal stem cells in psoriasis. Br J Dermatol 167:68–76
Campanati A, Gesuita R, Giannoni M, Piraccini F, Sandroni L, Martina E, Conocchiari L, Bendia E, Di Sario A, Offidani A (2013) Role of small intestinal bacterial overgrowth and Helicobacter pylori infection in chronic spontaneous urticaria: a prospective analysis. Acta Derm Venereol 93:161–164
Campanati A, Ganzetti G, Di Sario A, Benedetti A, Offidani A (2013) Insulin resistance, serum insulin and HOMA-R. J Gastroenterol 48:673
Campanati A, Ganzetti G, Di Sario A, Damiani A, Sandroni L, Rosa L, Benedetti A, Offidani A (2013) The effect of etanercept on hepatic fibrosis risk in patients with non-alcoholic fatty liver disease, metabolic syndrome, and psoriasis. J Gastroenterol 48:839–846
Campanati A, Moroncini G, Ganzetti G, Pozniak KN, Goteri G, Giuliano A, Martina E, Liberati G, Ricotti F, Gabrielli A, Offidani A (2013) Adalimumab modulates angiogenesis in psoriatic skin. Eur J Inflamm 11:489–498
Carrascosa JM, Rocamora V, Fernandez-Torres RM, Jimenez-Puya R, Moreno JC, Coll-Puigserver N, Fonseca E (2014) Obesity and psoriasis: inflammatory nature of obesity, relationship between psoriasis and obesity, and therapeutic implications. Actas Dermosifiliogr 105:31–44
de Groot M, Teunissen MB, Ortonne JP, Lambert JR, Naeyaert JM, Picavet DI, Arreaza MG, Simon JS, Kraan M, Bos JD, de Rie MA (2007) Expression of the chemokine receptor CCR5 in psoriasis and results of a randomized placebo controlled trial with a CCR5 inhibitor. Arch Dermatol Res 299:305–313
De Simone C, Amerio P, Amoruso G, Bardazzi F, Campanati A, Conti A, Gisondi P, Gualdi G, Guarneri C, Leoni L, Loconsole F, Mazzotta A, Musumeci ML, Piaserico S, Potenza C, Prestinari F (2013) Immunogenicity of anti-TNFα therapy in psoriasis: a clinical issue? Expert Opin Biol Ther 13:1673–1682
Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Prockop Dj, Horwitz E (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8:315–317
Ekman AK, Sigurdardottir G, Carlström M, Kartul N, Jenmalm MC, Enerbäck C (2013) Systemically elevated Th1-, Th2- and Th17-associated chemokines in psoriasis vulgaris before and after ultraviolet B treatment. Acta Derm Venereol 93:527–531
Eysteinsdóttir JH, Sigurgeirsson B, Ólafsson JH, Fridriksson T, Agnarsson BA, Davíðsson S, Valdimarsson H, Lúðvíksson BR (2013) The role of Th17/Tc17 peripheral blood T cells in psoriasis and their positive therapeutic response. Scand J Immunol 78:529–537
Ganzetti G, Campanati A, Offidani A (2012) Alopecia areata: a possible extraintestinal manifestation of Crohn’s disease. J Crohns Colitis 6:962–963
Garcia-Rodriguez S, Arias-Santiago S, Perandrés-López R, Castellote L, Zumaquero E, Navarro P, Buendía-Eisman A, Ruiz JC, Orgaz-Molina J, Sancho J, Zubiaur M (2013) Increased gene expression of Toll-like receptor 4 on peripheral blood mononuclear cells in patients with psoriasis. J Eur Acad Dermatol Venereol 27:242–250
Gigante A, Manzotti S, Bevilacqua C, Orciani M, Di Primio R, Mattioli-Belmonte M (2008) Adult mesenchymal stem cells for bone and cartilage engineering: effect of scaffold materials. Eur J Histochem 52:169–174
Halfon S, Abramov N, Grinblat B, Ginis I (2011) Markers distinguishing mesenchymal stem cells from fibroblasts are downregulated with passaging. Stem Cells Dev 20:53–66
Harper EG, Guo C, Rizzo H, Lillis JV, Kurtz SE, Skorcheva I, Purdy D, Fitch E, Iordanov M, Blauvelt A (2009) Th17 cytokines stimulate CCL20 expression in keratinocytes in vitro and in vivo: implications for psoriasis pathogenesis. J Invest Dermatol 129:2175–2183
He Z, Jin L, Liu ZF, Hu L, Dang EL, Feng ZZ, Li QJ, Wang G (2012) Elevated serum levels of interleukin 21 are associated with disease severity in patients with psoriasis. Serum IL-21 levels in patients with psoriasis are elevated and positively correlate with PASI scores. Br J Dermatol 167:191–193
Heidenreich R, Röcken M, Ghoreschi K (2009) Angiogenesis drives psoriasis pathogenesis. Int J Exp Pathol 90:232–248
Hou R, Yan H, Niu X, Chang W, An P, Wang C, Yang Y, Yan X, Li J, Liu R, Li X, Zhang K (2014) Gene expression profile of dermal mesenchymal stem cells from patients with psoriasis. J Eur Acad Dermatol Venereol. doi:10.1111/jdv.12420
Hughes M, Chinoy H (2013) Successful use of tocilizumab in a patient with psoriatic arthritis. Rheumatology (Oxford) 52:1728–1729
Kempuraj D, Conti P, Vasiadi M, Alysandratos KD, Tagen M, Kalogeromitros D, Kourelis T, Gregoriou S, Makris M, Stavrianeas NG, Theoharides TC (2010) IL-32 is increased along with tryptase in lesional psoriatic skin and is up-regulated by substance P in human mast cells. Eur J Dermatol 20:865–867
Krueger J, Bowcock A (2005) Psoriasis pathophysiology: current concepts of pathogenesis. Ann Rheum Dis 64:ii30–ii36
Lazzarini R, Olivieri F, Ferretti C, Mattioli-Belmonte M, Di Primio R, Orciani M (2014) mRNAs and miRNAs profiling of mesenchymal stem cells derived from amniotic fluid and skin: the double face of the coin. Cell Tissue Res 355:121–130
Michalak-Stoma A, Bartosińska J, Kowal M, Juszkiewicz-Borowiec M, Gerkowicz A, Chodorowska G (2013) Serum levels of selected Th17 and Th22 cytokines in psoriatic patients. Dis Markers 35:625–631
Michalak-Stoma A, Pietrzak A, Szepietowski JC, Zalewska-Janowska A, Paszkowski T, Chodorowska G (2011) Cytokine network in psoriasis revisited. Eur Cytokine Netw 22:160–168
Orciani M, Emanuelli M, Martino C, Pugnaloni A, Tranquilli AL, Di Primio R (2008) Potential role of culture mediums for successful isolation and neuronal differentiation of amniotic fluid stem cells. Int J Immunopathol Pharmacol 21:595–602
Orciani M, Mariggiò MA, Morabito C, Di Benedetto G, Di Primio R (2010) Functional characterization of calcium-signaling pathways of human skin-derived mesenchymal stem cells. Skin Pharmacol Physiol 23:124–132
Orciani M, Gorbi S, Benedetti M, Di Benedetto G, Mattioli-Belmonte M, Regoli F, Di Primio R (2010) Oxidative stress defense in human-skin-derived mesenchymal stem cells versus human keratinocytes: Different mechanisms of protection and cell selection. Free Radic Biol Med 49:830–838
Orciani M, Campanati A, Salvolini E, Lucarini G, Di Benedetto G, Offidani A, Di Primio R (2011) The mesenchymal stem cell profile in psoriasis. Br J Dermatol 165:585–592
Orciani M, Svegliati S, Gorbi S, Spadoni T, Lazzarini R, Regoli F, Di Primio R, Gabrielli A (2013) Alterations of ROS pathways in scleroderma begin at stem cell level. J Biol Regul Homeost Agents 27:211–224
Puig L, López A, Vilarrasa E, García I (2013) Efficacy of biologics in the treatment of moderate-to-severe plaque psoriasis: a systematic review and meta-analysis of randomized controlled trials with different time points. J Eur Acad Dermatol Venereol. doi:10.1111/jdv.12238
Raychaudhuri SP (2013) Role of IL-17 in psoriasis and psoriatic arthritis. Clin Rev Allergy Immunol 44:183–193
Salvolini E, Lucarini G, Zizzi A, Orciani M, Di Benedetto G, Di Primio R (2010) Human skin-derived mesenchymal stem cells as a source of VEGF and nitric oxide. Arch Dermatol Res 302:367–374
Salvolini E, Orciani M, Lucarini G, Vignini A, Tranquilli AL, Di Primio R (2011) VEGF and nitric oxide synthase immunoexpression in Down’s syndrome amniotic fluid stem cells. Eur J Clin Invest 41:23–29
Swindell WR, Xing X, Stuart PE, Chen CS, Aphale A, Nair RP, Voorhees JJ, Elder JT, Johnston A, Gudjonsson JE (2012) Heterogeneity of inflammatory and cytokine networks in chronic plaque psoriasis. PLoS ONE 7:e34594
van den Reek JM, van Lümig PP, Otero ME, Zweegers J, van de Kerkhof PC, Ossenkoppele PM, Njoo MD, Mommers JM, Koetsier MI, Arnold WP, Sybrandy-Fleuren BA, Kuijpers AL, Andriessen MP, Seyger MM, Kievit W, de Jong EM (2014) Satisfaction with medication is high for biologics in psoriasis. Results from the BioCAPTURE network. Br J Dermatol. doi:10.1111/bjd.12862
Wollina U, Unger L, Heinig B, Kittner T (2010) Psoriatic arthritis. Dermatol Ther 23:1231–1236
Yeung H, Takeshita J, Mehta NN, Kimmel SE, Ogdie A, Margolis DJ, Shin DB, Attor R, Troxel AB, Gelfand JM (2013) Psoriasis severity and the prevalence of major medical comorbidity: a population-based study. JAMA Dermatol 149:1173–1179
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This work was supported by grant FIRB-RBAP10MLK7_003 from Ministero dell’Istruzione, dell’Università e della Ricerca, Rome, Italy.
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A. Campanati and M. Orciani contributed equally to this work.
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Campanati, A., Orciani, M., Consales, V. et al. Characterization and profiling of immunomodulatory genes in resident mesenchymal stem cells reflect the Th1-Th17/Th2 imbalance of psoriasis. Arch Dermatol Res 306, 915–920 (2014). https://doi.org/10.1007/s00403-014-1493-3
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DOI: https://doi.org/10.1007/s00403-014-1493-3