title: Carbon monoxide exposure improves immune function in lupus-prone mice.
abstract: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multiple alterations affecting the normal function of immune cells, such as lymphocytes, dendritic cells (DCs) and monocytes. Although the understanding of autoimmunity has significantly increased, the breakthrough in effective therapies has been modest, making necessary the development of new therapeutic strategies. Here we propose that a new potential target for therapy is haem oxygenase-1 (HO-1), an enzyme that catalyses the degradation of the haem group into biliverdin, carbon monoxide (CO) and Fe(2+) . These products exhibit immunosuppressive and anti-inflammatory effects, which can contribute to improving tolerance during organ transplantation. Because HO-1 is highly expressed by immune cells involved in SLE pathogenesis, such as monocytes and DCs, we evaluated whether induction of HO-1 expression or the administration of CO could ameliorate disease in the FcγRIIb knockout (KO) mouse model for SLE. We found that CO administration decreased the expansion of CD11b(+) cells, prevented the decline of regulatory T cells and reduced anti-histone antibodies observed in untreated FcγRIIb KO mice. Furthermore, CO-treated animals and HO-1 induction showed less kidney damage compared with untreated mice. These data suggest that HO-1 modulation and CO administration can ameliorate autoimmunity and prevent the lupus symptoms shown by FcγRIIb KO mice, highlighting HO-1 as a potential new target for autoimmune therapy.
authors.affiliation: Millennium Institute on Immunology and Immunotherapy, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Juan P
authors.initials: JP
authors.lastname: Mackern-Oberti
authors.forename: Carolina
authors.initials: C
authors.lastname: Llanos
authors.forename: Leandro J
authors.initials: LJ
authors.lastname: Carreño
authors.forename: Sebastián A
authors.initials: SA
authors.lastname: Riquelme
authors.forename: Sergio H
authors.initials: SH
authors.lastname: Jacobelli
authors.forename: Ignacio
authors.initials: I
authors.lastname: Anegon
authors.forename: Alexis M
authors.initials: AM
authors.lastname: Kalergis
mesh_terms: D000818:Animals; D015551:Autoimmunity / Q000187:drug effects; D039481:CD11b Antigen / Q000378:metabolism; D002248:Carbon Monoxide / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D051547:Heme Oxygenase-1 / Q000096:biosynthesis; D007668:Kidney / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000201:enzymology / Q000276:immunology* / Q000628:therapy*; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017452:Receptors, IgG / Q000172:deficiency / Q000235:genetics; D013154:Spleen / Q000276:immunology / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology
chemical_list: D039481:CD11b Antigen; C499172:Fcgr2b protein, mouse; D008565:Membrane Proteins; D017452:Receptors, IgG; D002248:Carbon Monoxide; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse
keywords: carbon monoxide; haem oxygenase-1; systemic lupus erythematosus