Comparison and immunobiological characterization of retinoic acid inducible gene-I-like receptor expression in mesenchymal stromal cells

• Published in: Scientific reports 2017-06, Vol.7 (1), p.2896-14, Article 2896
• Main Authors: Raicevic, Gordana, Najar, Mehdi, Busser, Hélène, Crompot, Emerence, Bron, Dominique, Toungouz, Michel, Lagneaux, Laurence
• Format: Article
• Language: English
• Subjects: 13/1; 13/100; 13/106; 13/109; 13/2; 13/21; 13/31; 38; 631/250/251; 631/250/254; 631/532/2074; 82/1; 82/79; Acids; Adipose tissue; Apoptosis; Cell Survival - genetics; Cytokines - metabolism; DEAD Box Protein 58 - genetics; DEAD Box Protein 58 - metabolism; Gene expression; Gene Expression Regulation; Hematology; Humanities and Social Sciences; Humans; I-kappa B Kinase - metabolism; Immunomodulation; Immunophenotyping; Infections; Inflammation; Inflammatory diseases; Interferon regulatory factor 7; Interferon Regulatory Factor-7 - metabolism; Interferon-Induced Helicase, IFIH1 - genetics; Interferon-Induced Helicase, IFIH1 - metabolism; Leukemia Inhibitory Factor - genetics; Leukemia Inhibitory Factor - metabolism; Melanoma; Mesenchymal stem cells; Mesenchymal Stem Cells - metabolism; Mesenchyme; multidisciplinary; Organ Specificity; Pathogens; Phosphorylation; Poly I-C - pharmacology; Polyinosinic:polycytidylic acid; Receptors, Immunologic; Receptors, Retinoic Acid - genetics; Receptors, Retinoic Acid - metabolism; Retinoic acid; RNA, Messenger - genetics; Science; Science (multidisciplinary); Stem cells; Stromal cells; TLR3 protein; TNF-Related Apoptosis-Inducing Ligand - genetics; TNF-Related Apoptosis-Inducing Ligand - metabolism; Toll-Like Receptor 3 - metabolism; Toll-like receptors; Transplantation; Viral infections
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-02850-6

Due to their immunomodulatory and regenerative properties, Mesenchymal stromal cells (MSC) have generated major interests in several clinical settings including transplantation and inflammatory diseases. MSC functions can be influenced by their tissue origin. Their microenvironment strongly affects their biology notably through TLR sensing. In this study, we show that MSC isolated from four different sources express another type of cytosolic pathogen recognition receptors known as retinoic acid inducible gene-I (RIG-I)-like receptors (RLR). RLR activation in MSC induces the production of Type I IFN (IFN-β) and Type III IFN (IFN-λ1). The highest producers are adipose tissue(AT)-MSC. We further show that Interferon production is induced through TBK1/IKK-ε signaling and IRF7 phosphorylation. Depending on MSC source, the knockdown of TLR3 and/or RIG-I decreases the MSC response to RLR ligand poly(I:C)/Lyovec. Among the different MSC types, AT-MSCs display the highest sensitivity to viral stimuli as shown by the alteration of their viability after prolonged stimulation. Our work indicates that this could be linked to an increase of pro-apoptotic Noxa expression. Finally, the expression of IDO1 and LIF upon RLR activation indicate the increase of MSC immunomodulatory potential, especially in AT-MSCs. Altogether, these data should be considered when designing MSC-based therapy in clinical settings where inflammation or infection are present.