Mesenchymal stem cells in psoriatic lesions affect the skin microenvironment through circular RNA

Psoriasis is an autoimmune skin disease. Our previous studies revealed abnormal immune regulation of skin mesenchymal stem cells (S-MSCs) in psoriatic lesions. Circular RNA (circRNA) molecules were recently discovered as a new class of non-coding regulatory RNAs. Their role in the pathogenesis of psoriasis has not yet been studied. To explore potential circRNA-mediated mechanisms of S-MSCs in the pathogenesis of psoriasis, we sequenced mRNAs and circRNAs of MSCs from normal skin and psoriatic lesions, followed by functional prediction and interaction analyses. In total, 129 circRNAs were differentially expressed, including 123 up-regulated and 6 down-regulated circRNAs, in MSCs from psoriatic lesions. Pathway analysis showed that the genes significantly down-regulated in psoriatic as compared to normal S-MSCs were mainly involved in JAK-STAT signalling. According to a circRNA-miRNA-mRNA interaction network, the expression of circRNAs associated with these mRNAs was also down-regulated in MSCs of psoriatic skin lesions. Knockdown of the circRNA gene chr2:206992521|206994966 reduced the capacity of S-MSCs to inhibit T-cell proliferation upon co-culture in normal as well as lesion-derived S-MSCs. Secreted-cytokine profiles (IL-6, IL-11 and hepatocyte growth factor) were also similar in normal and lesion-derived S-MSCs after circRNA knockdown. Thus, the circRNA chr2:206992521|206994966 in S-MSCs from psoriatic lesions affects the activity of T lymphocytes in local lesions by influencing their cytokine secretion. Taken together, our findings indicate that circRNA mediates the role of S-MSCs in the pathogenesis of psoriasis.