Characteristics Of Circulating T Follicular Helper Cells And Their Subsets In Patients With Psoriasis Vulgaris

Objective:To investigate the characteristics of T follicular helper(Tfh)cells,functional molecular expressions on Tfh cells,Tfh cell subsets,CD19+B cells and IL-21R expression on CD19+B cells in patients with psoriasis vulgaris,and their associations with disease severity.In addition,the change of Tfh cells frequency and some functional molecular expressions on Tfh cells before and after 1-month treatment were also observed.To explore the function and significance of Tfh cells in the pathogenesis of psoriasis,we also investigated whether IL-21,main functional cytokine of Tfh cells,could induce CD4+T cells to differentiate into T helper 17 cells(Th17)in psoriasis,and the relationship between Tfh 17 cell frequency and IL-21R expression on CD 19+B cells in psoriasis patients.Method:The frequencies of Tfh cells,functional markers(ICOS,PD-1,HLA-DR,Ki-67,IL-21,IL-17,IFN-y,IL-10)of Tfh cells,subsets(Tfh1,Tfh2,Tfh17)of Tfh cells,CD19+B cells and IL-21R expression on CD 19+B cells were compared by using flow cytometry between 32 patients with psoriasis vulgaris and 13 healthy controls.The infiltration of Tfh cells in normal skin tissues,lesional and non-lesional skin tissues of psoriasis patients were detected by using immunohistochemistry and immunofluorescence.Severity of the psoriasis was evaluated by Psoriasis Area and Severity Index(PASI)score.Then the correlations between the frequencies of Tfh cells,Tfh cell subsets and PASI score were analyzed.The relationship between the number of Tfh cells in psoriasis lesions and PASI score was analyzed as well.Besides,we also investiageted the correlation between Tfh17 cell frequency and IL-21R expression on CD 19+B cells in psoriasis patients.Moreover,the dynamic changes of Tfh cells frequency and some cytokines secreted by Tfh cells before and after 1-month treatment in moderate to severe patients were evaluated.To further address the function of Tfh cells in the pathogenesis of psoriasis,we cultured purified CD4+ T cells from patients with psoriasis vulgaris and healthy controls with or without IL-21(main functional cytokine of Tfh cells)in vitro,then observed whether IL-21 could induce CD4+T cells to differentiate into Th17 cells.Results:Our results showed both increased frequency and activation(indicated by higher expression of ICOS,PD-1,HLA-DR,Ki-67 and increased production of IL-21,IL-17 and IFN-y)of cTfh cells in psoriasis patients(P<0.05).However,the level of IL-10 secreted by Tfh cells demonstrated no significant difference between psoriasis patients and healthy normals(P>0.05).In addition,the frequency of Tfh17 cell subset and(Tfhl 7+ Tfh2)/Tfh1 ratio were also significantly increased in patients with psoriasis(P<0.05),while the frequencies of Tfhl cells and Tfh2 cells showed no difference between psoriasis group and healthy control group(P>0.05).Moreover,both of the frequency of Tfh cells and the frequency of Tfh17 cell subset were positively correlated with PASI score.Our data also showed that although the frequency of CD 19+ B cells showed no significant difference between the two groups(P>0.05),the level of IL-21R expression on CD 19+ B cells was significantly increased in patients with psoriasis vulgaris(P<0.05)and was associated with the PASI score.The expression of IL-21R on B cells had a positive correlation with the frequency of circulating Tfh17 cells in psoriasis as well.Besides,the number of Tfh cells in psoriasis lesions was significantly higher than that in non-lesional skin tissues of psoriasis(P<0.05),but there was no significant correlation between the number of infiltrating Tfh cells and PASI score in psoriasis patients.After 1-month treatment,Tfh cells frequency and the levels of cytokines(IL-21,IL-17,IFN-y)secreted by Tfh cells were all significantly decreased(P<0.05).In vitro,stimulation with IL-21 significantly increased the frequencies of Th17 cells among CD4+ T cells purified from patients with psoriasis vulgaris and healthy controls(P<0.05).Conclusion:Both of Tfh cells frequency and functional markers expressions on Tfh cells were increased in patients with psoriasis.Among Tfh cell subsets,only Tfh17 subset was increased in psoriasis patients and associated with PASI score and the expression of IL-21R on B cells.After 1-month treatment,accompanied with the alleviation of skin lesions,the frequency of Tfh cells was decreased.IL-21,the key functional cytokine of Tfh cells,could promote CD4+ T cells to differentiate into Th17 cells in psoriasis in vitro.These results indicated that Tfh cells may participate in the pathogenesis of psoriasis through inducing CD4+T cells to differentiate into Th17 cells and prompting B cells to be activated.Our data not only showed a new sight on the pathogenesis of psoriasis,but also provided a new potential therapeutic target of psoriasis.