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01-09-2010 | Original Paper

Expression of Th1 and Th2 cytokine-associated transcription factors, T-bet and GATA-3, in peripheral blood mononuclear cells and skin lesions of patients with psoriasis vulgaris

Authors: Kejian Zhu, Jun Ye, Miao Wu, Hao Cheng

Published in: Archives of Dermatological Research | Issue 7/2010

Abstract

Psoriasis is considered as a T cell-mediated autoimmune disease, and the Th1 response has been established as the major immune agent in its pathomechanisms. The relative expression of Th1 and Th2 transcription factors, T-bet and GATA-3, resulting in a swing in the Th1/Th2 pendulum, has been implicated in a number of immunological diseases. However, their expression and correlation with psoriasis has not yet been studied. Our aim was to evaluate the expression of T-bet and GATA-3 in psoriatic patients and determine their correlation with serum levels of IFN-γ and IL-4. Sera, peripheral blood mononuclear cells (PBMCs) and skin lesions were taken from 23 patients with psoriasis vulgaris. Serum levels of IFN-γ and IL-4 were measured by ELISA. T-bet and GATA-3 mRNA expression in PBMCs was analyzed by RT-PCR. Lesional expression and distribution of CD4, CD8, T-bet and GATA-3 were assessed by immunohistochemistry. Blood and skin samples of healthy individuals served as controls. A markedly higher IFN-γ and lower IL-4 concentration in the serum of psoriatic patients was found. A significantly higher expression of T-bet mRNA and a lower expression of GATA-3 mRNA in PBMCs, and consequently, a much higher T-bet/GATA-3 ratio in patients than in controls were shown. T-bet mRNA expression was strongly correlated with serum IFN-γ secretion in patients; furthermore, the correlation between T-bet/GATA-3 ratio and IFN-γ/IL-4 ratio was revealed. We also observed a significant increase in CD4+ cells and T-bet positive cells in psoriatic lesions. These results suggested that T-bet and GATA-3 might be regulator genes for psoriasis via the Th1/Th2 balance, and the Th1-specific transcription factor, T-bet, may play an important role in the development and maintenance of psoriasis.

Arakawa S, Hatano Y, Katagiri K (2004) Differential expression of mRNA for Th1 and Th2 cytokine-associated transcription factors and suppressors of cytokine signaling in peripheral blood mononuclear cells of patients with atopic dermatitis. Clin Exp Immunol 135:505–510CrossRefPubMed

Arican O, Aral M, Sasmaz S, Ciragil P (2005) Serum levels of TNF-α, IFN-γ, IL-6, IL-8, IL-12, IL-17 and IL-18 in patients with active psoriasis and correlation with disease severity. Mediat Inflamm 5:273–279CrossRef

Austin LM, Ozawa M, Kikuchi T, Walters IB, Krueger JG (1999) The majority of epidermal T cells in psoriasis vulgaris lesions can produce type 1 cytokines, interferon γ, interleukin-2, and tumor necrosis factor-α, defining TC1 (cytotoxic T lymphocyte) and Th1 effector populations: a type 1 differentiation bias is also measured in circulating blood T cells in psoriatic patients. J Invest Dermatol 113:752–759CrossRefPubMed

Baker BS, Swain AF, Fry L, Valdimarsson H (1984) Epidermal T lymphocytes and HLA-DR expression in psoriasis. Br J Dermatol 110:55–64CrossRef

Barker JN (1998) Psoriasis as a T-cell-mediated autoimmune disease. Hosp Med 59:530–533PubMed

Bata-Csorgo Z, Hammemberg C, Voorhees JJ, Cooper KD (1993) Flow cytometric identification of proliferative subpopulations within normal human epidermis and the localization of the primary hyperproliferative population in psoriasis. J Exp Med 178:1271–1281CrossRefPubMed

Boss JD, Hagenaars C, Das PK, Krieg SR, Voorn WJ, Kapsenberg ML (1989) Predominance of memory T cells (CD4+, CDw29+) over naive T cells (CD4+, CD45R+) in both normal and diseased human skin. Arch Dermatol Res 281:24–30CrossRef

Farrar JD, Asnagli H, Murphy KM (2002) T helper subset development: roles of instruction, selection, and transcription. J Clin Invest 109:431–435PubMed

Finotto S (2008) T-cell regulation in asthmatic diseases. Chem Immunol Allergy 94:83–92CrossRefPubMed

10.

Frisullo G, Angelucci F, Caggiula M, Nociti V, Iorio R, Patanella AK, Sancricca C, Mirabella M, Tonali PA, Batocchi AP (2006) pSTAT1, pSTAT3, and T-bet expression in peripheral blood mononuclear cells from relapsing-remitting multiple sclerosis patients correlates with disease activity. J Neurosci Res 84:1027–1036CrossRefPubMed

11.

Ghoreschi K, Mrowietz U, Röcken M (2003) A molecule solves psoriasis? Systemic therapies for psoriasis inducing interleukin 4 and Th2 responses. J Mol Med 81:471–480CrossRefPubMed

12.

Ghoreschi K, Thomas P, Breit S, Dugas M, Mailhammer R, van Eden W, van der Zee R, Biedermann T, Prinz J, Mack M, Mrowietz U, Christophers E, Schlöndorff D, Plewig G, Sander CA, Röcken M (2003) Interleukin-4 therapy of psoriasis induces Th2 responses and improves autoimmune disease. Nat Med 9:40–46CrossRefPubMed

13.

Glimcher LH (2001) Lineage commitment in lymphocytes: controlling the immune response. J Clin Invest 108:25–30

14.

Jain S, Kaur IR, Das B, Bhattachrya SN, Singh A (2009) T helper 1 to T helper 2 shift in cytokine expression: an autoregulatory process in superantigen-associated psoriasis progression? J Med Microbiol 58:180–184CrossRefPubMed

15.

Kawashima M, Miossec P (2005) mRNA quantification of T-bet, GATA-3, IFN-γ, and IL-4 shows a defective Th1 immune response in the peripheral blood from rheumatoid arthritis patients: link with disease activity. J Clin Immunol 25:209–214CrossRefPubMed

16.

Krueger JG (2002) The immunologic basis for the treatment of psoriasis with new biologic agents. J Am Acad Dermatol 46:1–23CrossRefPubMed

17.

Lantelme E, Mantovani S, Palermo B, Campanelli R, Sallusto F, Giachino C (2001) Kinetics of GATA-3 gene expression in early polarizing and committed human T cells. Immunology 102:123–130CrossRefPubMed

18.

Lee HJ, Takemoto N, Kurata H, Kamogawa Y, Miyatake S, O’Garra A, Arai N (2000) GATA-3 induces T helper cell type 2 (Th2) cytokine expression and chromatin remodeling in committed Th1 cells. J Exp Med 192:105–115CrossRefPubMed

19.

Lynch GW, Slaytor EK, Elliott FD, Saurajen A, Turville SG, Sloane AJ, Cameron PU, Cunningham AL, Halliday GM (2003) CD4 is expressed by epidermal Langerhans’ cells predominantly as covalent dimers. Exp Dermatol 12:700–711CrossRefPubMed

20.

Macaubas C, Lee PT, Smallacombe TB, Holt BJ, Wee C, Sly PD, Holt PG (2002) Reciprocal patterns of allergen-induced GATA-3 expression in peripheral blood mononuclear cells from atopics vs non-atopics. Clin Exp Allergy 32:97–106CrossRefPubMed

21.

Mosmann TR, Cherwinski H, Bond MW, Giedlin MA, Coffman RL (1986) Two types of murine helper T cell clone I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol 136:2348–2357PubMed

22.

Mueller W, Hermann B (1979) Cyclosporin A for psoriasis. N Engl J Med 301:555PubMed

23.

Mullen AC, High FA, Hutchins AS, Lee HW, Villarino AV, Livingston DM, Kung AL, Reiner SL (2001) Role of T-bet in commitment of TH1 cells before IL-12-dependent selection. Science 292:1907–1910CrossRefPubMed

24.

Nickolof BJ (1999) Skin innate immune system in psoriasis: friend or foe? J Clin Invest 104:1161–1164CrossRef

25.

Noble A (2000) Molecular signals and genetic reprogramming in peripheral T-cell differentiation. Immunology 101:29–289CrossRef

26.

Ozawa M, Aiba S (2004) Immunopathogenesiss of psoriasis. Curr Drug Targets Inflamm Allergy 3:137–144CrossRefPubMed

27.

Park H, Lee CM, Jung ID, Lee JS, Jeong YI, Chang JH, Chun SH, Kim MJ, Choi IW, Ahn SC, Shin YK, Yeom SR, Park YM (2009) Quercetin regulates Th1/Th2 balance in a murine model of asthma. Int Immunopharmacol 9:261–267CrossRefPubMed

28.

Pietrzak AT, Zalewska A, Chodorowska G, Krasowska D, Michalak-Stoma A, Nockowski P, Osemlak P, Paszkowski T, Rolinski JM (2008) Cytokines and anticytokines in psoriasis. Clin Chim Acta 394:7–21CrossRefPubMed

29.

Pincelli C, Lotti R (2009) What’s new in laboratory research? J Rheumatol Suppl 83:17–18CrossRefPubMed

30.

Placek W, Haftek M, Thivolet J (1988) Sequence of changes in psoriatic epidermis. Immunocompetent cell redistribution precedes altered expression of keratinocyte differentiation markers. Acta Derm Venereol 68:369–377PubMed

31.

Rao A, Avni O (2000) Molecular aspects of T-cell differentiation. Br Med Bull 56:969–984CrossRefPubMed

32.

Sabat R, Philipp S, Hoflich C, Kreutzer S, Wallace E, Asadullah K, Volk HD, Sterry W, Wolk K (2007) Immunopathogenesis of psoriasis. Exp Dermatol 16:779–798CrossRefPubMed

33.

Schlaak JF, Buslau M, Jochum W, Hermann E, Girndt M, Gallati H, Meyer zum Buschenfelde KH, Fleischer B (1994) T cells involved in psoriasis vulgaris belong to the Th1 subset. J Invest Dermatol 102:145–149CrossRefPubMed

34.

Szabo SJ, Kim ST, Costa GL, Zhang X, Fathman CG, Glimcher LH (2000) A novel transcription factor, T-bet, directs Th1 lineage commitment. Cell 100:655–669CrossRefPubMed

35.

Szabo SJ, Sullivan BM, Stemmann C, Satoskar AR, Sleckman BP, Glimcher LH (2002) Distinct effects of T-bet in TH1 lineage commitment and IFN-gamma production in CD4 and CD8 T cells. Science 295:338–342CrossRefPubMed

36.

Williams EJ, Haque S, Bank SC, Johnson P, Sarsfield P, Sheron N (2000) Distribution of the interleukin-8 receptors, CXCR1 and CXCR2, in inflamed gut tissue. J Pathol 192:533–539CrossRefPubMed

Title: Expression of Th1 and Th2 cytokine-associated transcription factors, T-bet and GATA-3, in peripheral blood mononuclear cells and skin lesions of patients with psoriasis vulgaris
Authors: Kejian Zhu
Jun Ye
Miao Wu
Hao Cheng
Publication date: 01-09-2010
Publisher: Springer-Verlag
Published in: Archives of Dermatological Research / Issue 7/2010
Print ISSN: 0340-3696
Electronic ISSN: 1432-069X
DOI: https://doi.org/10.1007/s00403-010-1048-1

2024 ASCO Annual Meeting

Springer Medicine

Expression of Th1 and Th2 cytokine-associated transcription factors, T-bet and GATA-3, in peripheral blood mononuclear cells and skin lesions of patients with psoriasis vulgaris

Abstract

2024 ASCO Annual Meeting

Springer Medicine

Abstract

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