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

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