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Blood, 1 September 2005, Vol. 106, No. 5, pp. 1694-1702.
Prepublished online as a Blood First Edition Paper on May 26, 2005; DOI 10.1182/blood-2005-02-0494.
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IMMUNOBIOLOGY
Heme oxygenase-1 expression inhibits dendritic cell maturation and proinflammatory function but conserves IL-10 expression
Christine Chauveau,
Séverine Rémy,
Pierre Joseph Royer,
Marcelo Hill,
Séverine Tanguy-Royer,
François-Xavier Hubert,
Laurent Tesson,
Régis Brion,
Gaëlle Beriou,
Marc Gregoire,
Régis Josien,
Maria Cristina Cuturi, and
Ignacio Anegon
From the Institut National de la Santé et de la Recherche Médicale (INSERM) Unit 643 and Institut de Transplantation et de Recherche en Transplantation (ITERT), Nantes, France; and INSERM U601, Nantes, France.
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. (Blood. 2005;106:1694-1702)
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