Background
Various cytokines have been indicated to be involved in the pathogenesis of systemic sclerosis (SSc). IL-22 is one of the member of IL-10 cytokine family, and several studies have implicated IL-22 signaling in the pathogenesis of autoimmune diseases. Objectives: To clarify the role of IL-22 in the regulatory mechanism of ECM expression and to determine the contribution of IL-22 to the phenotype of SSc.
Conclusion
IL-22 expressed in infiltrated lymphocytes may stimulate the up-regulation of type I collagen protein in dermal fibroblasts via let-7a down-regulation in SSc skin.
Methods
The effect of IL-22 on ECM expression in normal fibroblasts was determined by using PCR array, real-time PCR and immunoblotting. microRNA expression was evaluated by real-time PCR. The expression levels of IL-22 in the skin and sera were determined by using immunohistochemical staining and ELISA.
Results
IL-22 significantly increased the expression of type I collagen protein without changing its mRNA levels in cultured normal human dermal fibroblast. The expression of let-7a, one of the microRNAs which have negative effect on type I collagen expression, was significantly decreased by the treatment with IL-22 in dermal fibroblasts. There was no significant difference in the serum levels of IL-22 between SSc patients and control subjects. However, the expression of IL-22 was detected in the infiltrated lymphocytes in the SSc dermis, but not in normal dermis. IL-22 receptors were expressed in both normal and SSc dermal fibroblasts to the similar extent.