title: Heme oxygenase-1 expression inhibits dendritic cell maturation and proinflammatory function but conserves IL-10 expression.
abstract: Heme oxygenase-1 (HO-1) is an intracellular enzyme that degrades heme and inhibits immune responses and inflammation in vivo. In most cell types, HO-1 is inducible by inflammatory stimuli and oxidative stress. Here we demonstrate that human monocyte-derived immature dendritic cells (iDCs) and several but not all freshly isolated rat splenic DC subsets and rat bone marrow-derived iDCs, spontaneously express HO-1. HO-1 expression drastically decreases during human and rat DC maturation induced in vitro. In human tissues, iDCs also express HO-1, whereas mature DCs do not. Induction of HO-1 expression with cobalt protoporphyrin (CoPP) in human and rat DCs inhibits lipopolysaccharide (LPS)-induced phenotypic maturation and secretion of proinflammatory cytokines, resulting in the inhibition of alloreactive T-cell proliferation. CoPP-treated DCs, however, retain the ability to produce the anti-inflammatory cytokine interleukin 10 (IL-10). Reactive oxygen species induced by LPS in DCs were inhibited by induction of HO-1. In conclusion, we identify, for the first time, the capacity of HO-1 to block maturation of DCs and to inhibit proinflammatory and allogeneic immune responses while preserving IL-10 production. This novel immune function for HO-1 may be of interest for the inhibition of immune responses in autoimmune diseases, transplantation, and other conditions involving activation of the immune system.
authors.affiliation: INSERM U643, CHRU Nantes, 30 boulevard Jean Monnet, 44093 Nantes, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Chauveau
authors.forename: Séverine
authors.initials: S
authors.lastname: Rémy
authors.forename: Pierre Joseph
authors.initials: PJ
authors.lastname: Royer
authors.forename: Marcelo
authors.initials: M
authors.lastname: Hill
authors.forename: Séverine
authors.initials: S
authors.lastname: Tanguy-Royer
authors.forename: François-Xavier
authors.initials: FX
authors.lastname: Hubert
authors.forename: Laurent
authors.initials: L
authors.lastname: Tesson
authors.forename: Régis
authors.initials: R
authors.lastname: Brion
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Beriou
authors.forename: Marc
authors.initials: M
authors.lastname: Gregoire
authors.forename: Régis
authors.initials: R
authors.lastname: Josien
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Cuturi
authors.forename: Ignacio
authors.initials: I
authors.lastname: Anegon
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D051547:Heme Oxygenase-1; D006801:Humans; D007249:Inflammation / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008565:Membrane Proteins; D011524:Protoporphyrins / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D011524:Protoporphyrins; D016753:Interleukin-10; C007095:cobaltiprotoporphyrin; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1