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

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Journal of Translational Medicine201210 (Suppl 3) :P48

  • Published:


  • Arthritis
  • Cationic Liposome
  • Th17 Lymphocyte
  • Monocyte Subset
  • Inflammatory Monocyte


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.

Authors’ Affiliations

INSERM, U844 Montpellier, France
University of Medicine, Montpellier, France
UFR des Sciences Pharmaceutiques et Biologiques, INSERM, U1022 Paris, France
CNRS, UMR8151 Paris, France
University of Pharmacy Paris Descartes, Paris, France
Ecole Nationale Supérieure de Chimie de Paris, Paris, France
University Hospital of Montpellier, Clinical Dept. for osteoarticular diseases, Montpellier, France
Center of Experimental Rheumatology, University Hospital Zurich and Zurich Center of Integrative Human Physiology, Zurich, Switzerland


© Présumey et al; licensee BioMed Central Ltd. 2012

This article is published under license to 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.