In Cellulo and In Vivo Comparison of Cholesterol, Beta-Sitosterol and Dioleylphosphatidylethanolamine for Lipid Nanoparticle Formulation of mRNA

International audienceLipid Nanoparticles (LNPs) are a leading class of mRNA delivery systems. LNPs are made of an ionizable lipid, a polyethyleneglycol (PEG)-lipid conjugate and helper lipids. The success of LNPs is due to proprietary ionizable lipids and appropriate helper lipids. Using a benchmark lipid (D-Lin-MC3) we compared the ability of three helper lipids to transfect dendritic cells in cellulo and in vivo. Studies revealed that the choice of helper lipid does not influence the transfection efficiency of immortalized cells but, LNPs prepared with DOPE (dioleylphosphatidylethanolamine) and β-sitosterol were more efficient for mRNA transfection in murine dendritic cells than LNPs containing DSPC (distearoylphosphatidylcholine). This higher potency of DOPE and β-sitosterol LNPs for mRNA expression was also evident in vivo but only at low mRNA doses. Overall, these data provide valuable insight for the design of novel mRNA LNP vaccines

miR-21-3p/IL-22 axes are major drivers of psoriasis pathogenesis by modulating keratinocytes proliferationsurvival balance and inflammatory response

International audiencePsoriasis 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-κB 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

miR-21-3p/IL-22 Axes Are Major Drivers of Psoriasis Pathogenesis by Modulating Keratinocytes Proliferation-Survival Balance and Inflammatory Response

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-κB 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

Plateforme MO2VING: from MOlecular Organization to in Vivo ImagiNG

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