This article is part of the supplement: 7th European Workshop on Immune-Mediated Inflammatory Diseases

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NAMPT/Visfatin expression by inflammatory monocytes mediates arthritis pathogenesis by promoting IL-17–producing T cells

Jessy Présumey12, Gabriel Courties12, Pascale Louis-Plence12, Virginie Escriou3456, Daniel Scherman3456, Yves-Marie Pers127, Hans Yssel12, Jérôme Pène12, Diego Kyburz8, Steffen Gay8, Christian Jorgensen127 and Florence Apparailly127*

  • * Corresponding author: Florence Apparailly

Author Affiliations

1 INSERM, U844, Montpellier, France

2 University of Medicine, Montpellier, France

3 INSERM, U1022, UFR des Sciences Pharmaceutiques et Biologiques, Paris, France

4 CNRS, UMR8151, Paris, France

5 University of Pharmacy Paris Descartes, Paris, France

6 Ecole Nationale Supérieure de Chimie de Paris, Paris, France

7 University Hospital of Montpellier, Clinical Dept. for osteoarticular diseases, Montpellier, France

8 Center of Experimental Rheumatology, University Hospital Zurich and Zurich Center of Integrative Human Physiology, Zurich, Switzerland

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Journal of Translational Medicine 2012, 10(Suppl 3):P48  doi:10.1186/1479-5876-10-S3-P48

The electronic version of this article is the complete one and can be found online at:

Published:28 November 2012

© 2012 Présumey et al; licensee BioMed Central Ltd.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Nicotinamide phosphoribosyltransferase (NAMPT)/PBEF/Visfatin exerts multiple functions and has been implicated in the pathogenesis of rheumatoid arthritis. The expression of NAMPT is increased during inflammation and is identified as a novel mediator of innate immunity. To gain insight into its role in arthritis and given that NAMPT induces IL-6 expression that is critical for Th17 lymphocytes, we hypothesized that NAMPT-stimulated production of IL-6 by monocytes might in turn promote Th17 cells.

Materials and methods

siRNA uptake and NAMPT expression were determined in Ly6Chigh and Ly6Clow monocyte subsets following intravenous injection of siRNA against NAMPT (siNAMPT) or non-targeting siRNA (siCT) formulated with the DMAPAP cationic liposome into mice. Mice with established collagen-induced arthritis (CIA) were treated weekly after disease onset with siNAMPT or siCT and clinical features were assessed. T helper cell frequencies, cytokine production and percentage of IL-6-producing Ly6Chigh monocytes were analyzed. Using a coculture system consisting of purified CD14+ monocytes and autologous CD4+ T cells, NAMPT and cytokine production, as well as the percentage of IL-17-producing CD4+ T cells were determined following transfection of CD14+ monocytes with siCT or siNAMPT.


Upon intravenous injection, siRNA was preferentially engulfed by Ly6Chigh monocytes and siRNA-mediated silencing of NAMPT expression in Ly6Chigh monocytes reduced IL-6 production by these cells, mitigated Th17 cell expansion, and inhibited inflammatory features and CIA progression. Moreover, NAMPT-RNAi-silenced CD14+ monocytes were found to reduce the percentage of IL-17-producing CD4+ T cells.


Taken together, our results show that the expression of NAMPT in Ly6Chigh monocytes promotes Th17 cells. Our findings provide new mechanistic insight into the action of NAMPT in arthritis and demonstrate the utility of targeting disease-causing genes in Ly6Chigh monocytes for therapeutic intervention in arthritis.