Analysis of Th1/Th2 response pattern for erythrodermic psoriasis

Abstract

As one of the most serious types of psoriasis, pathogenesis of erythrodermic psoriasis (EP) is unclear so far. In this study, we aimed to detect the levels of Th1/Th2 cytokine-associated transcription factors and T-lymphocyte clone in peripheral blood mononuclear cells (PBMCs) derived from EP patients, and gene expression level of T-bet/GATA-3 in skin lesion. The potential role of Th1/Th2 reaction pattern played in the pathogenesis of EP was also discussed. Serum levels of IFN-γ, IL-2, IL-4 and IL-10 were quantified by ELISA among 16 EP patients, 20 psoriasis vulgaris (PV) patients and 15 healthy controls. The expression levels of T-bet/GATA-3 in the skin lesion and PBMCs were examined by real-time qPCR. The ratio of Th1/Th2 was measured by flow cytometry. The levels of IFN-γ, IL-2, IL-4 and IL-10 were higher in EP patients than in the healthy controls. The levels of IL-4 and IL-10 were 69.44±11.45 and 12.62±4.57 pg/mL, respectively, in EP patients, significantly higher than those in PV patients and healthy controls (P<0.05). Flow cytometry revealed the levels of both Th1 and Th2 in PBMCs from EP patients were higher than those in healthy controls, and the Th1/Th2 ratio was dramatically lower than in PV patients (P<0.01). The ratios of IFN-γ/IL-4 and T-bet/GATA-3 in EP patients were both less than 1.0, suggesting a reversal when compared with the other two groups. Our study indicated that the EP patients exerted a Th1/Th2 bidirectional response pattern, and the balance of Th cell subsets inclines to Th2, which might be one of the important mechanisms of EP pathogenesis.

Keywords

erythrodermic psoriasis / Th1/Th2 cell / T-bet/GATA-3 / cytokine

References

[1] RosenbachM, HsuS, KormanNJ, et al.. Treatment of erythrodermic psoriasis: from the medical board of the National Psoriasis Foundation. J Am Acad Dermatol, 2010, 62(4): 655-662

[2] ZattraE, Belloni FortinaA, PesericoA, et al.. Erythroderma in the era of biological therapies. Eur J Dermatol, 2012, 22(2): 167-171

[3] ZhuK, YeJ, WuM, et al.. 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. Arch Dermatol Res, 2010, 302(7): 517-523

[4] EyerichS, OnkenAT, WeidingerS, et al.. Mutual antagonism of T cells causing psoriasis and atopic eczema. N Engl J Med, 2011, 365(3): 23

[5] BrandtEB, SivaprasadU. Th2 cytokines and atopic dermatitis. Clin Cell Immunol, 2011, 2(3): 110

[6] LiLF, SujanSA, YangH, et al.. Serum immunoglobulins in psoriatic erythroderma. Clin Exp Dermatol, 2005, 30(2): 125-127

[7] NickoloffBJ. The immunologic and genetic basis of psoriasis. Arch Dermatol, 1999, 135(9): 1104-1110

[8] SzegediA, AlekszaM, GondaA, et al.. Elevated rate of T-helper 1 (Th1) lymphocytes and serum IFN-gamma levels in psoriatic patients. Immunol Lett, 2003, 86(3): 277-280

[9] CousinsDJ, LeeTH, StaynovDZ. Cytokine coexpression during human Th1/Th2 cell differentiation: direct evidence for coordinated expression of Th2 cytokines. J Immunol, 2002, 169: 2498-2506

[10] AbdallahMA, Abdel-HamidMF, KotbAM, et al.. Serum interferon-gamma is a psoriasis severity and prognostic marker. Cutis, 2009, 84(3): 163-168

[11] LeeRE, GaspariMT, LotzeAE, et al.. Interleukin-2 and psoriasis. Arch Dermatol, 2001, 124: 1811-1815

[12] ZalewskaA, WyczółkowskaJ, Dziankowska-BartkowiakB, et al.. Interleukin 4 plasma levels in psoriasis vulgaris patients. Med Sci Monit, 2004, 10(4): CR156-162

[13] MichelG, MirmohammadsadeghA, OllasE, et al.. Demonstration and functional analysis of IL-10 receptors in human epidermal cells: decreased expression in psoriation by an antipsoriatc gluccocorticoid in normal cultured keratinocytes. J Immunol, 1997, 159: 6291-6297

[14] AsadullahK, SterryW, StephanekK, et al.. IL-10 is a key cytokine in psoriasis. Proof of principle by IL-10 therapy: a new therapeutic approach. J Clin Invest, 1998, 101(4): 783-794

[15] SmartJM, HorakE, KempAS, et al.. Polyclonal and allergen-induced cytokine responses in adults with asthma: resolution of asthma is associated with normalization of IFN-gamma responses. J Allergy Clin Immunol, 2002, 110(3): 450-456

[16] ArakawaS, HatanoY, KatagiriK. 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, 2004, 135: 505-510

[17] GhoreschiK, MrowietzU, RöckenM. A molecule solves psoriasis? Systemic therapies for psoriasis inducing interleukin 4 and Th2 responses. J Mol Med (Berl), 2003, 81(8): 471-480

[18] LametschwandtnerG, BiedermannT, SchwarzlerC, et al.. Sustained T-bet expression confers polarized human TH2 cells with TH1-like cytokine production and migratory capacities. J Allergy Clin Immunol, 2004, 113: 987-994

[19] SekiN, MiyazakiM, SuzukiW, et al.. IL-4 induced GA-TA-3 expression is a time-restricted instruction switch for Th2 cell differentiation. J Immunol, 2004, 172: 6158-6166

[20] HultgrenOH, AverringM, StokowskiA. T-box transcription-factor-deficient mice display increased joint pathology and failure of infection control during staphylococcal arthritis. Microbes Infect, 2004, 6(6): 529-535