The Significance And Expression Of Th17 Cell In Patients With Psoriasis

Psoriasis is a commonly seen chronic inflammatory disease which is easily recur and hard to treat. Its morbidity rate is about 1-3%, and keep increasing in recent years. Because of the reduplicated recurrences of this disease, it needs to be treated again and again, thus causing heavy burden to the patients and their family whose physical and mental health are greatly influent by the burden. The cause of this disease is complicated and its pathogenesis is still unknown. At present, the pathogenesis is assumed to be related to immune, heredity, psychology, and environment factors. The main pathology of psoriasis is abnormal proliferation of keratinocyte, parakeratosis, neovascularization and inflammatory cell infiltration. Current common view is that the pathology of psoriasis is a kind of thymus derived cell mediated dermatitis which is polygenic inheritance and caused by multi-factors. Its pathogenesis is complicated, the abnormity of CD4+T lymphocyte immunologic function is the most important. The CD4+T lymphocyte is categorized into Th1 and Th2. Th1 cytokines such as IFN-γand IL-12 influent the clean up of parasite and extracellular bacteria. IFN-γand IL-12 are symbolic cytokine of Th1 and Th2 cell subpopulation, respectively. Th17 cell, a new kind of CD4+T cell subpopulation is found recently, highly convey IL-17, and excrete IL-6 and TNF-α. Th17 has independent differentiate and growth regulatory mechanism which play an important role in immunological and infectious disease. It is a hot topic for debate currently. And IL-23R is a key factor to Th17 cell. IL-23 is applied to Th17 cell to maintain its expression. It is approved that IL-23 stimulate the amplification and maintain of Th17 cell, and the differentiation of Th17 in human bodies depend on IL-1βand IL-23. Therefore, IL-23R is a key factor to Th17 cell subpopulation. The pathogenicity of IL-23, IL-23R, TH17, IL-17 in autoimmune disease has been approved. Recent research showed that the IL-17mRNA could be detected at the skin lesions of psoriasis, while could't be detected at nonlesion. This result showed that Thl7 cell is exist at the skin lesions of psoriasis, and it play an important role in the pathology of psoriasis. Recently, the role of Th17 cell in the pathology of psoriasis is attracting more and more people's attention. Th17 has become one of the international hot debates of research.This research is to evaluated the expression of Th17 cell on peripheral blood PBMC in patient with psoriasis, and its relationship and meaning of clinical psoriasis. This paper also observes the influence of MTX on Th17 cell and related cytokine in psoriasis. The possible mechanism of MTX's treatment in psoriasis is also being discussed. Furthermore, identifying the variant area of IL-23R gene related to psoriasis in Han ethnic group population, and discussing the relationship between genetic polymorphism and susceptibility of psoriasis in Han ethnic group.There are three sections following:Section 1:Analysis on the change of Th17 cell in psoriasis vulgaris patient's peripheral blood and its clinical relationship and meaning of psoriasisObjective:To study the expression of psoriasis patient's Th17 cell in peripheral blood and its clinical relationships, preliminary definitude the mechanism and clinical meaning of Th17 cell on pathology of psoriasis.Methods:Forty-three patients with psoriasis vulgaris, and 30 healthy control were sequentially enrolled in this study. Expression of peripheral blood mononuclear cells CD4 (+) IL-17(+) were detected by flow cytometry. Analysis the differences between the active stage group, rest stage group and control group.Results:The chromosome of flow cell shows that the number of PBMC CD4 (+) IL-17(+) cell in patient group is much more than healthy control. The PBMC CD4 (+) IL-17(+) expression of patients at active stage is higher than those at rest stage (F=142.34, P<0.001). Moreover, the PBMC CD4 (+) IL-17(+) expression of patients has positive correlation its severity index PASI.Conclusions:The number of psoriasis patient's peripheral blood Th17 cell increased, the number of Th17 has positive correlation with the severity index of common psoriasis. Th17 may play an important role in the pathology of psoriasis. The Th17 targeted therapy may become a new effective way to treat psoriasisSection2:The examination of Th17 cell and its related cytokine in the skin lesions and peripheral blood of patient with psoriasis vulgaris, as well as the clinical meaning of the examinationObjective:To detect the IL-17, IL-23 expression level of Th17 and its related cytokine in the skin lesions and peripheral blood of patient with psoriasis vulgaris.To identify the clinical meaning of serum level test and the Th17 cell expression differences between psoriasis patients, normal people or patient at different stage. To observe the influence of MTX on the expression of Th17 and its related cytokines, and discuss the role of Th17 cell on the pathology of psoriasis and the mechanism of MTX treatment to psoriasis vulgaris.Methods:The level of IL-17 and IL-23 in peripheral blood and skin lesions before and after MTX treatment were detected by ELISA and nested polymerase chain reaction. the The changes of IL-17 and IL-23 were observed dynamically before and after treatment. The relation between the change and the BASDI of patients with psoriasis vulgaris were analyzed.Results:(1) The expression of IL-17mRNA, IL-23mRNA in the skin lesions of patients with psoriasis vulgaris are higher than that of healthy control (P<0.001). And the level of patient at active stage is higher than those at rest stage. (P<0.001). After 8 weeks of MTX treatment, the skin lesions are improved, the expression of IL-17mRNAN,IL-23mRNA in the skin lesions obviously lower than that before treatment (P<0.001). But there is no statistic difference with healthy control (P>0.05)(2) The serum concentration of patients with psoriasis vulgaris is obvious higher than that of healthy control(P<0.001).The peripheral blood level of IL-17, IL-23 are related to the periodization of psoriasis vulgaris. And the level of patient at active stage is higher than those at rest stage. (P<0.05). After 8 weeks of MTX treatment, the serum concentration level of IL-17, IL-23 is lower than that before treatment (P<0.001). But there is no statistic difference with healthy control (P>0.05).(3) The expression of IL-17mRNA,IL-23mRNA in the skin lesions of patients with psoriasis vulgaris is related to the severity index PASI of psoriasis vulgaris (r= 0.469, P=0.0112). The serum concentration change of IL-17, IL-23 is related to the severity index PASI of psoriasis vulgaris (r=0.732,0.611, P<0.05)Conclusions:(1) The results show that the expression of Th17 cell and its related cytokine IL-17, IL-23 in the peripheral blood and skin lesions of patients with psoriasis vulgaris are higher than that of healthy control. Moreover, the IL-17, IL-23 cytokine expression level of the patients at active stage is higher than those at rest stage, which means the related cytokine of Th17 cell, may play an important role in the pathology of psoriasis vulgaris.(2) MTX can adjust the immune system of psoriasis patients through the function of Th17 cell. This may be one of the function mechanisms to cure psoriasis.Section3 Research on the IL-23R single nucleotide polymorphism of psoriasis patients in Han ethnic groupObjective:Research on the relation between the genetic polymorphism of interleukin-23 receptor (IL-23R) and the psoriasis susceptibility in Han ethnic group.Methods:Search 7 SNP locus of IL-23R(rs11209026,rs1004819,rs10489629,rs1343151,rs10889677.rs11209032.rs1495965) in NCBI databas(http://www.ncbi.nlm.nih.gov/). Ninty-three patients with psoriasis from outpatient and 108 healthy control were enrolled in this study. The relation of 7 SNP locus and psoriasis susceptibility in 201 samples were analyzed. The data processing of polymorphism, haplotype and psoriasis relative risks are all deal with SPSS software. Results:The rate of 4 allelic genes among 7 TagSNP locus (rs1004819. rs1343151.rs10889677.rs1495965) vary differently between the patients group and the control group(P<0.001)Conclusions:IL-23R gene polymorphism is related to the psoriasis susceptibility. The SNP (rs1004819.rs1343151.rs10889677.rs1495965) have a strong relation with the pathology of psoriasis...