The Expression Of Interferon-?,Interleukin-17 And Interleukin-22 In Human Oral Lichen Planus

Background and Objective:Oral lichen planus(OLP)is one of the more common oral mucosal diseases,which affects 0.5-2%of the population worldwide.The clinical manifestations of OLP are white striation,erythema,erosion,papules,plaques and ulcers.On the pathology,OLP is characterized by a dense subepithelial infiltration of lymphocytes and the degeneration of basal keratinocytes.Although a lot of research progressed on OLP,the etiology of OLP remains unclear,the efficacy of OLP is not ideal.Much evidence shows that T cell-mediated immune response and immune disorders that a variety of inflammatory molecules participated have played an important role in the pathogenesis of OLP.IFN-?,Thl cell signature cytokine,has been reported to play an important role in the basal keratinocyte apoptosis of OLP.IL-17,significant cytokine of Th17 cell induces the keratinocytes to selectively produce various inflammatory mediators,which compose the complex immune network in the inflammatory environment of OLP lesions.IL-22 is the significant cytokine of Th22 cells,which is considered to be a newly found CD4+Th subset.IL-22 has recently been reported to be involved in the pathogenesis of autoimmune and inflammatory disorders such as psoriasis,lupus erythematosus,and rheumatoid arthritis with IFN-y and IL-17.Only one study published that investigated the association between IL-22 and the pathogenesis of OLP,only investigated the expression of IL-22 in OLP,but the different expression of IL-22 between different clinical types and the correlation with other cytokines had not yet detected.Therefore,the aim of this study is to investigate the role cytokine interferon-y,interleukin-17 and interleukin-22 played in tissues formation and and development of human OLP.In addition,we will also evaluate the correlation of the three cytokines and further explore the pathological mechanism of OLP,so as to provide train of thought for the clinical treatment of OLP.Methods:The tissues of 15 cases of normal oral epithelium and 36 cases of OLP(16 erosion and 20 non-erosion)were investigated for the expression of IFN-y,IL-17and IL-22 proteins by using Envision two-step method of immunohistochemistry in order to analyze the correlations between the expressions of these three cytokines,and their clinical and pathological characteristics in OLP.The level of cytokines IFN-?,IL-17and IL-22 in peripheral blood were detected by ELISA in 30 OLP patients(including 14 erosive cases and 16 non-erosive cases),and 12 healthy volunteers who served as controls.The differences of the expression levels of IFN-y,IL-17and IL-22 in different OLP groups and those of the control group were statistically analyzed.Result:1.In the connection analysis of OLP pathological characteristics,a positive correlation was found between the degree of basal keratinocytes degeneration and basal keratinocytes degeneration in the connection analysis of OLP pathological characteristics(Spearman r=0.480,P=0.003).2.By immunohistochemistry,compared with the normal group,the expression levels of IFN-y,IL-17,IL-22 in the erosion OLP group and non-erosion OLP group was significantly higher(P<0.05).But there was no significant difference between the two different OLP groups.Only the expression level of IFN-y in OLP local lesions and the degree of lymphocytes infiltration had a positive correlation(Spearman r=0.426,P=0.01).In addition,there was a positive correlation in expression levels of IFN-y,IL-17 and IL-22 in OLP local lesions and the degree of basal keratinocytes degeneration(Spearman r=0.693,P<0.01),(Spearman r=0.411,P<0.05)and(Spearman r=0.425,P=0.01).There is no positive correlation between IFN-y and IL-17 proteins in OLP,but a positive correlation was found between IL-17 and IL-22 proteins in OLP(Spearman r=0.368,P=0.027).A positive correlation was also found between IFN-?and IL-22 proteins in OLP(Spearman r=0.354,P=0.034).3.By ELISA,the levels of IFN-?,IL-17,IL-22 in erosion OLP were found significantly higher than the normal group(P<0.05),while no statistical differences were seen in non-erosive OLP and the normal group(P>0.05).Conclusion:1.In the correlation analysis of OLP pathological characteristics,a positive correlation was found between the degree of basal keratinocytes degeneration and basal keratinocytes degeneration.It was demonstrated that cytotoxicity of lymphocytes infiltration could trigger keratinocyte apoptosis so as to cause deogeneration of basal keratinocytes.2.Compared with the normal group,the higher levels of IFN-?,IL-17,IL-22 in OLP local lesions suggested that these cytokines played a crucial role in immune regulation and immune-mediated function of pathogenesis of OLP;a positive correlation was found between the expression levels of IFN-y,IL-17,IL-22 in OLP local lesions and the degree analysis of OLP pathological characteristics,which could reveal that these cytokines play an important role in pathological injury of OLP.These results provided more evidence for a very close relationship between these cytokines and the development of this disease.IFN-y,IL-17and IL-22 proteins in OLP local lesions had a positive correlation shows that they could participate in pathogenesis of OLP with common cooperation in a cytokine network.3.The levels of IFN-y,IL-17,IL-22 in erosion OLP were found significantly higher than the normal group(P<0.05),which showed us the erosive form of OLP with systemic immune disorder and abnormal immune response led to a more active phase of the disease.And these cytokines play a more important role in erosion OLP.