Carbon Monoxide Inhibits TLR-Induced Dendritic Cell Immunogenicity

S. Remy, P. Blancou, L. Tesson, V. Tardif, R. Brion, P. J. Royer, R. Motterlini, R. Foresti, M. Painchaut, S. Pogu, M. Gregoire, J. M. Bach (+2 others)
2009 Journal of Immunology  
Heme oxygenase-1 (HO-1) exerts its functions via the catabolism of heme into carbon monoxide (CO), Fe 2؉ , and biliverdin, as well as by depletion of free heme. We have recently described that overexpression of HO-1 is associated with the tolerogenic capacity to dendritic cells (DCs) stimulated by LPS. In this study, we demonstrate that treatment of human monocytederived DCs with CO blocks TLR3 and 4-induced phenotypic maturation, secretion of proinflammatory cytokines, and alloreactive T cell
more » ... lloreactive T cell proliferation, while preserving IL-10 production. Treatment of DCs with biliverdin, bilirubin, and deferoxamine or replenishing intracellular heme stores had no effect on DC maturation. HO-1 and CO inhibited LPS-induced activation of the IFN regulatory factor 3 pathway and their effects were independent of p38, ERK, and JNK MAPK. HO-1 and CO treatment also inhibited mouse DC maturation in vitro and mouse DC immunogenic properties in vivo, as shown by adoptive cell transfer in a transgenic model of induced diabetes. Thus, for the first time, our data show that CO treatment inhibits DC immunogenicity induced by TLR ligands and that blockade of IFN regulatory factor 3 is associated with this effect.
doi:10.4049/jimmunol.0802436 pmid:19201840 fatcat:2onslz5qkrajrhejxiqnbpnfmu