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Welsby I, Detienne S, N'Kuli F, et al. Lysosome-Dependent Activation of Human Dendritic Cells by the Vaccine Adjuvant QS-21. Front Immunol. 2017;7:663doi: 10.3389/fimmu.2016.00663.
Welsby, I., Detienne, S., N'Kuli, F., Thomas, S., Wouters, S., Bechtold, V., De Wit, D., Gineste, R., Reinheckel, T., Elouahabi, A., Courtoy, P. J., Didierlaurent, A. M., & Goriely, S. (2016). Lysosome-Dependent Activation of Human Dendritic Cells by the Vaccine Adjuvant QS-21. Frontiers in immunology, 7663. https://doi.org/10.3389/fimmu.2016.00663
Welsby, Iain, et al. "Lysosome-Dependent Activation of Human Dendritic Cells by the Vaccine Adjuvant QS-21." Frontiers in immunology vol. 7 (2016): 663. doi: https://doi.org/10.3389/fimmu.2016.00663
Welsby I, Detienne S, N'Kuli F, Thomas S, Wouters S, Bechtold V, De Wit D, Gineste R, Reinheckel T, Elouahabi A, Courtoy PJ, Didierlaurent AM, Goriely S. Lysosome-Dependent Activation of Human Dendritic Cells by the Vaccine Adjuvant QS-21. Front Immunol. 2017 Jan 05;7:663. doi: 10.3389/fimmu.2016.00663. eCollection 2016. PMID: 28105029; PMCID: PMC5215313.
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Front Immunol. 2017 Jan 05;7:663. doi: 10.3389/fimmu.2016.00663. eCollection 2016.

Lysosome-Dependent Activation of Human Dendritic Cells by the Vaccine Adjuvant QS-21.

Frontiers in immunology

Iain Welsby, Sophie Detienne, Francisca N'Kuli, Séverine Thomas, Sandrine Wouters, Viviane Bechtold, Dominique De Wit, Romain Gineste, Thomas Reinheckel, Abdelatif Elouahabi, Pierre J Courtoy, Arnaud M Didierlaurent, Stanislas Goriely

Affiliations

  1. Institute for Medical Immunology, Université Libre de Bruxelles (ULB) , Gosselies , Belgium.
  2. Cell Biology Unit, de Duve Institute, Université Catholique de Louvain , Brussels , Belgium.
  3. GSK Vaccines , Rixensart , Belgium.
  4. Medical Faculty, Institute for Molecular Medicine and Cell Research, Albert Ludwigs University , Freiburg , Germany.

PMID: 28105029 PMCID: PMC5215313 DOI: 10.3389/fimmu.2016.00663

Abstract

The adjuvant properties of the saponin QS-21 have been known for decades. It is a component of the Adjuvant System AS01 that is used in several vaccine candidates. QS-21 strongly potentiates both cellular and humoral immune responses to purified antigens, yet how it activates immune cells is largely unknown. Here, we report that QS-21 directly activated human monocyte-derived dendritic cells (moDCs) and promoted a pro-inflammatory transcriptional program. Cholesterol-dependent QS-21 endocytosis followed by lysosomal destabilization and Syk kinase activation were prerequisites for this response. Cathepsin B, a lysosomal cysteine protease, was essential for moDC activation

Keywords: adjuvant; cathepsins; cytokine; dendritic cells; lysosome; saponins; vaccine

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