Heme oxygenase-1 expression inhibits dendritic cell maturation and proinflammatory function but conserves IL-10 expression.
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.
Chauveau
Christine
C
INSERM U643, CHRU Nantes, 30 boulevard Jean Monnet, 44093 Nantes, France.
Rémy
Séverine
S
Royer
Pierre Joseph
PJ
Hill
Marcelo
M
Tanguy-Royer
Séverine
S
Hubert
François-Xavier
FX
Tesson
Laurent
L
Brion
Régis
R
Beriou
Gaëlle
G
Gregoire
Marc
M
Josien
Régis
R
Cuturi
Maria Cristina
MC
Anegon
Ignacio
I
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
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