Foxp3+ Regulatory T Cells And Related Cytokines Differentially Expressed And Functional Study In Plaque Versus Guttate Psoriasis

PartⅠFoxp3+ regulatory T cells differentially expressed in the skin lesions of plaque versus guttate psoriasisObjective To investigate the number of Foxp3+ cell in the skin lesions of psoriasis vulgaris in correlation with the severity of skin lesions and the subtype and staging of disease.Methods The number of Foxp3+ cell and the percentage of Foxp3+ cell among CD3+ cell were examined in the skin lesion of 41 patients with psoriasis vulgaris and 10 normal skin specimens as control by immunohistochemical single or double-staining technique. The severity of skin lesions biopsied and disease was evaluated by PSI scoring and PASI scoring, respectively.Results Foxp3+ cell in psoriatic lesions was predominantly located in papillary and upper reticular layers of dermis, minimally in epidermis, and it was absent or scant in perilesional normal-appearing skin and normal skin as control. The number of Foxp3+ cell in psoriatic lesions was positively correlated with the severity of skin lesions (PSI scoring) (p＜0.0001), and it was higher in plaque psoriasis than in guttate psoriasis, and in progressive stage higher than, and higher in stable stage than in regressive stage(p<0.05). The percentage of Foxp3+ cell among CD3+ cell was higher in papillary dermis than in epidermis and upper reticular layer of dermis(p<0.0001), and it was gradually declined from the center lesion to the border and perilesional normal-appearing skin.Conclusion The differential expression of Foxp3+ cell in plaque versus guttate psoriasis implicate their different stage of immunopathogenesis. The highest expression of Foxp3+ cell in papillary dermis and center lesion might participate in the initiation and maintenance of psoriasis vulgaris.Part II Treg and Th17 cells differentially expressed in peripheral blood of plaque versus guttate psoriasisObjective To investigate the level of Treg cell and Th17 cell in peripheral blood of psoriasis vulgaris in correlation with the subtype of disease.Methods The level of Foxp3+CD4+Treg cell and IL-17+CD4+Th17 cell among CD4+ cell in peripheral blood of 17 patients with psoriasis vulgaris and 12 normal controls was measured by flow cytometry. The percentage of aTreg, rTreg, non-Treg cell and the percentage of CD4+CD25high, CD4+CD25mid, CD4+CD251ow cell among CD4+CD25+T cell in 11 plaque psoriasis and normal controls were analyzed according to the expression of CD25 and CD45RA and the difference in strength of CD25 expression.Results The level of Foxp3+CD4+Treg cell in peripheral blood of psoriasis vulgaris was positively correlated with the severity of disease (PASI scoring) (p<0.05). The level of Foxp3+CD4+Treg cell in peripheral blood of plaque psoriasis was higher than in guttate psoriasis(p<0.0001); whereas, the level of IL-17+CD4+ Th17 cell was lower than in guttate psoriasis(p<0.0001). The percentage of CD4+CD25highTreg and aTreg in plaque psoriasis was obvious higher than normal controls(p<0.001, p<0.0001). The difference was statistically significant. The percentage of CD4+CD25+ cell in plaque psoriasis was higher than in normal controls(p<0.05); however, no significant difference in the percentage of rTreg, non-Treg cell and CD4+CD25mid, CD4+CD251ow cell was found between plaque psoriasis and normal controls.Conclusion The imbalance between of Treg and Thl7 cells play an important role in the pathogenesis of plaque versus guttate psoriasis.PartⅢThe difference in inhibitory function of Treg cell to inflammatory cytokines between plaque and guttate psoriasisObjective To investigate the inhibitory function of TGF-(3-Foxp3+iTreg cell in psoriasis vulgaris to inflammatory cytokines produced by CD4+CD25-T cells and the content of inflammatory cytokines in serum in correlation with the subtype of disease.Methods CD4+CD25-T cells with or without TGF-βstimulation were cultured for 5 days. The percentage of CD25+Foxp3+ cell in CD4+CD25-T cell stimulated with TGF-βwas detected by flow cytometry. The content of cytokines such as TNF-α, IL-6, IL-1β, IL-17 and IFN-y in serum and supernatants were determined by ELISA.Results The percentage of CD25+Foxp3+ cell among CD4+CD25-T cell stimulated with TGF-βin plaque psoriasis was significant higher than in guttate psoriasis and normal controls(p<0.0001), and in guttate psoriasis was higher than in normal controls(p<0.05). The difference was statistically significant. CD4+CD25-T cells in plaque psoriasis produced more TNF-a after stimulated with TGF-β; CD4+CD25-T cells in guttate psoriasis produced more IL-6 and IL-1β; however, the level of TNF-a, IL-6 and IL-1(3 produced by CD4+CD25-T cells in normal controls was reduced after stimulated with TGF-β. The level of IL-17 and IL-6 in serum of guttate psoriasis was higher than in plaque psoriasis; however, the level of TNF-a was lower than in plaque psoriasis.Conclusion The differential expression of inflammatory cytokines in serum and regulation of TGF-β-Foxp3+iTreg cells to inflammatory cytokines produced by CD4+CD25-T cells in plaque versus guttate psoriasis implicate their different immunopathogenesis.