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Anti-inflammatory and immunosuppressive activation of human monocytes by a bioactive dendrimer

Abstract : The monocyte-macrophage (MPhi) lineage can undergo different pathways of activation. The classical priming by IFN-gamma, then triggering by LPS, conducts MPhi toward proinflammatory responses, whereas the alternative activation by IL-4, IL-10, IL-13, or glucocorticoids directs them toward an anti-inflammatory, immunosuppressive phenotype. Recently, we have shown that synthetic phosphorus-containing dendrimers activate human monocytes. Here, we analyzed the gene expression of monocytes activated by an acid azabisphosphonic-capped, phosphorus-containing dendrimer by comparison with untreated monocytes. We found that 78 genes were up-regulated, whereas 62 genes were down-regulated. Analysis of these genes directed the hypothesis of an alternative-like, anti-inflammatory activation of human monocytes. This was confirmed by quantitative RT-PCR and analysis of the surface expression of specific markers by flow cytometry. Functional experiments of inhibition of CD4(+) T-lymphocyte proliferation in MLR indicated that dendrimer-activated monocytes (da-monocytes) have an immune-suppressive phenotype similar to the one induced by IL-4. Moreover, da-monocytes preferentially enhanced amplification of CD4(+) T cells, producing IL-10, an immunosuppressive cytokine. Therefore, phosphorus-containing dendrimers appear as new nanobiotools promoting an anti-inflammatory and immunosuppressive activation of human monocytes and thus, prove to be good candidates for innovative, anti-inflammatory immunotherapies.
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https://www.hal.inserm.fr/inserm-02472254
Contributor : Mary Poupot <>
Submitted on : Monday, February 10, 2020 - 10:06:36 AM
Last modification on : Wednesday, July 15, 2020 - 5:05:21 PM

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Séverine Fruchon, Mary Poupot, Ludovic Martinet, Cédric-Olivier Turrin, Jean-Pierre Majoral, et al.. Anti-inflammatory and immunosuppressive activation of human monocytes by a bioactive dendrimer. Journal of Leukocyte Biology, Society for Leukocyte Biology, 2009, 85 (3), pp.553-562. ⟨10.1189/jlb.0608371⟩. ⟨inserm-02472254⟩

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