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Nicotinamide phosphoribosyltransferase/visfatin expression by inflammatory monocytes mediates arthritis pathogenesis
  1. Jessy Présumey1,2,
  2. Gabriel Courties1,2,
  3. Pascale Louis-Plence1,2,
  4. Virginie Escriou3,4,5,6,
  5. Daniel Scherman3,4,5,6,
  6. Yves-Marie Pers1,2,7,
  7. Hans Yssel1,2,
  8. Jérôme Pène1,2,
  9. Diego Kyburz8,
  10. Steffen Gay8,
  11. Christian Jorgensen1,2,7,
  12. Florence Apparailly1,2,7
  1. 1INSERM, U844, University Hospital Saint Eloi, Montpellier, France
  2. 2University of Medicine, Montpellier, France
  3. 3INSERM, U1022, UFR des Sciences Pharmaceutiques et Biologiques, Paris, France
  4. 4CNRS, UMR8151, Paris, France
  5. 5Chemical and Genetic Pharmacology and Imaging Laboratory, Faculté de Pharmacie, Université Paris Descartes, Paris, France
  6. 6Ecole Nationale Supérieure de Chimie de Paris, Paris, France
  7. 7Clinical Department for Osteoarticular Diseases, University Hospital Lapeyronie, Montpellier, France
  8. 8Center of Experimental Rheumatology, University Hospital Zurich and Zurich Center of Integrative Human Physiology, Zurich, Switzerland
  1. Correspondence to Dr Florence Apparailly, INSERM, U844, CHU Saint Eloi, 80 rue Augustin Fliche, 34295 Montpellier cedex 5, France; florence.apparailly{at}


Objectives Nicotinamide phosphoribosyltransferase (NAMPT)/pre-B-cell colony-enhancing factor/visfatin exerts multiple functions and has been implicated in the pathogenesis of rheumatoid arthritis. To gain insight into its role in arthritis and given that NAMPT is identified as a novel mediator of innate immunity, we addressed the function of monocyte-derived NAMPT in experimental arthritis by selective gene knockdown in inflammatory monocytes.

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 analysed. Using a co-culture system consisting of purified CD14 monocytes and autologous CD4 T cells, NAMPT and cytokine production, and the percentage of IL-17-producing CD4 T cells, were determined following transfection of CD14 monocytes with siCT or siNAMPT.

Results On intravenous injection, siRNA was preferentially engulfed by Ly6Chigh monocytes, and siRNA-mediated silencing of NAMPT expression in Ly6Chigh monocytes inhibited CIA progression. This effect was associated with reduced IL-6 production by Ly6Chigh monocytes, reduced proportion of Th17 cells and autoantibody titers, and decreased activation and infiltration of monocytes/macrophages and neutrophils in arthritic joints. Moreover, NAMPT-RNAi-silenced CD14 monocytes were found to reduce the percentage of IL-17-producing CD4 T cells in vitro.

Conclusions Our results show that the expression of NAMPT in Ly6Chigh monocytes promotes many downstream effects involved in inflammatory arthritis and demonstrate the utility of targeting disease-causing genes, such as NAMPT, in Ly6Chigh monocytes for therapeutic intervention in arthritis.

  • Arthritis
  • Cytokines
  • Inflammation
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