miR-21-3p/IL-22 axes are major drivers of psoriasis pathogenesis by modulating keratinocytes proliferation-survival balance and inflammatory response Abdallah, F. Henriet, E. Suet, A. Arar, A. Clemencon, R. Malinge, J. M. /Lecellier, Gael Baril, P. Pichon, C. IL-22 miR-21-5p miR-21-3p keratinocytes psoriasis proliferation Psoriasis is a chronic inflammatory skin disease that is mediated by complex crosstalk between immune cells and keratinocytes (KCs). Emerging studies have showed a specific psoriatic microRNAs signature, in which miR-21 is one of the most upregulated and dynamic miRNAs. In this study, we focused our investigations on the passenger miR-21-3p strand, which is poorly studied in skin and in psoriasis pathogenesis. Here, we showed the upregulation of miR-21-3p in an IMQ-induced psoriasiform mouse model. This upregulation was correlated with IL-22 expression and functionality, both in vitro and in vivo, and it occurred via STAT3 and NF-kappa B signaling. We identified a network of differentially expressed genes involved in abnormal proliferation control and immune regulatory genes implicated in the molecular pathogenesis of psoriasis in response to miR-21-3p overexpression in KCs. These results were confirmed by functional assays that validated the proliferative potential of miR-21-3p. All these findings highlight the importance of miR-21-3p, an underestimated miRNA, in psoriasis and provide novel molecular targets for therapeutic purposes.</p> 2021 text https://www.documentation.ird.fr/hor/fdi:010083303 fdi:010083303 Abdallah F., Henriet E., Suet A., Arar A., Clemencon R., Malinge J. M., Lecellier Gael, Baril P., Pichon C.. miR-21-3p/IL-22 axes are major drivers of psoriasis pathogenesis by modulating keratinocytes proliferation-survival balance and inflammatory response. 2021, 10 (10), 2547 [22 p.] EN