Expressions Of Chemokine CCL20 And Its Receptor CCR6 In The Serum And Skin Lesions Of Patients With Systemic Sclerosis

Objective:To investigate the expressions of chemokine CCL20 and its receptor CCR6 in the serum and skin lesions of patients with systemic sclerosis (SSc), trying to find the role of CCL20-CCR6 axis in the pathogenesis of SSc. To explore if there’s any new pathway in the pathogenesis of SSc, and the expressions of CCL20 may be a possible chemokine which is closely related to the severity and prognosis of this disease. In the long term, we hope to find a new target therapy for SSc.Methods:Case-control study was applied. We divided the case group into dcSSc group and lcSSc group. A total of 43 patients diagnosed with SSc were collected from the out-patient department of dermatology in the Peking Union Medical College Hospital (PUMCH) from November,2015 to May,2016.40 controls were enrolled from the physical examination center of PUMCH from March to April in 2016. We got 2-4 ml blood using EDTA anticoagulant of each person of these groups, and the serum was separated through centrifugation. First of all, we analyzed the demography, clinical manifestations and laboratory examination of the clinical data, aiming to evaluate the distribution of the age and sex, the multiorgan involvement and the autoantibodies of these patients. Using ELISA method we detected the expressions of CCL20 and IL-17 in these groups, and compared the statistically significance through the SNK-q test. Furthermore, we draw a scatter diagram and showed the correlation of CCL20 and IL-17 by calculating the correlation coefficient in both dcSSc group and lcSSc group. Finally, by using the method of immunohistochemical staining, we analyzed the expressions of CCR6 in the skin lesions and ultimately, explored the biological functions of CCL20-CCR6 axis in SSc disease.Results:We described and analyzed the demography, clinical manifestations and laboratory examination of the clinical data. Using the ELISA method we found that the expressions level of CCL20 in the serum of both dcSSc group and lcSSc group were higher than that of control group, and the difference was statistically significant(P<0.01). But the expression of CCL20 in lcSSc group was higher than that of dcSSc group (P＜0.05). The expressions level of IL-17 in the serum of both dcSSc group and lcSSc group were higher than that of control group, and the difference was statistically significant(P<0.01), but there is no significance in the expressions of IL-17 of dcSSc group and lcSSc group. By using the linear fitting, we found that the expression of CCL20 was closely related to the expression of IL-17 in the dcSSc group (r=0.73). While in the lcSSc group, the expression of CCL20 was not related to the expression of IL-17. At last, we stained the skin lesions of SSc and normal nipple skin tissues by using the immunohistochemical staining, and found that CCR6 only expressed in the skin lesions of SSc. We further defined the biological functions of CCL20-CCR6 axis in the pathogenesis of SSc.Conclusions:By binding with its receptor CCR6, CCL20 is involved in the pathogenesis of SSc through the chemotaxis of inflammatory cells migrating to the skin tissues, causing the skin changes in SSc. CCL20 and IL-17 are collaborative in the inflammation of dcSSc. Glucocorticoids may inhibit the effect of CCL20-CCR6 axis, and have an anti-inflammatory effect. The expression level of CCL20 can be used to evaluate the severity in SSc patients.