title: Carbon monoxide inhibits T cell activation in target organs during systemic lupus erythematosus.
abstract: Systemic lupus erythematosus is characterized by the presence of circulating anti-nuclear antibodies (ANA) and systemic damage that includes nephritis, haematological manifestations and pulmonary compromise, among others. Although major progress has been made in elucidating the molecular mechanisms responsible for autoimmunity, current therapies for lupus have not improved considerably. Because the exposure of carbon monoxide (CO) has been shown to display beneficial immunoregulatory properties in different immune-mediated diseases, we investigated whether CO therapy improves lupus-related kidney injury in lupus mice. MRL-Fas(lpr) lupus mice were exposed to CO and disease progression was evaluated. ANA, leucocyte-infiltrating populations in spleen, kidney and lung and kidney lesions, were measured. CO therapy significantly decreased the frequency of activated B220(+) CD4(-) CD8(-) T cells in kidneys and lungs, as well as serum levels of ANA. Furthermore, we observed that CO therapy reduced kidney injury by decreasing proliferative glomerular damage and immune complexes deposition, decreased proinflammatory cytokine production and finally delayed the impairment of kidney function. CO exposure ameliorates kidney and lung leucocyte infiltration and delays kidney disease in MRL-Fas(lpr) lupus mice. Our data support the notion that CO could be explored as a potential new therapy for lupus nephritis.
authors.affiliation: Millennium Institute on Immunology and Immunotherapy, Pontificia Universidad Católica de Chile, Santiago, Chile.|Departamento de Microbiología y Genética Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.|Institute of Medicine and Experimental Biology of Cuyo (IMBECU), Science and Technology Center (CCT) of Mendoza, National Council of Scientific and Technical Research (CONICET), Mendoza, Argentina.
authors.forename: J P
authors.initials: JP
authors.lastname: Mackern-Oberti
authors.affiliation: Millennium Institute on Immunology and Immunotherapy, Pontificia Universidad Católica de Chile, Santiago, Chile.|Departamento de Inmunología Clínica y Reumatología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: J
authors.initials: J
authors.lastname: Obreque
authors.affiliation: Departamento de Anatomía Patológica, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: G P
authors.initials: GP
authors.lastname: Méndez
authors.affiliation: Millennium Institute on Immunology and Immunotherapy, Pontificia Universidad Católica de Chile, Santiago, Chile.|Departamento de Inmunología Clínica y Reumatología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: C
authors.initials: C
authors.lastname: Llanos
authors.affiliation: Millennium Institute on Immunology and Immunotherapy, Pontificia Universidad Católica de Chile, Santiago, Chile.|Departamento de Microbiología y Genética Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.|Departamento de Inmunología Clínica y Reumatología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Pontificia Universidad Católica de Chile, Santiago, Chile.|INSERM UMR 1064-Center for Research in Transplantation and Immunology, Nantes, France.
authors.forename: A M
authors.initials: AM
authors.lastname: Kalergis
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D000936:Antigen-Antibody Complex / Q000276:immunology; D001323:Autoantibodies / Q000096:biosynthesis / Q000276:immunology; D002248:Carbon Monoxide / Q000494:pharmacology* / Q000627:therapeutic use; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D007678:Kidney Glomerulus / Q000166:cytology / Q000276:immunology / Q000293:injuries; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000276:immunology; D008181:Lupus Nephritis / Q000628:therapy*; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D019463:Mice, Inbred MRL lpr; D020556:Neutrophil Infiltration / Q000276:immunology; D011507:Proteinuria / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000974:Antibodies, Antinuclear; D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D016207:Cytokines; D002248:Carbon Monoxide; D017493:Leukocyte Common Antigens
keywords: T cells; autoimmunity; carbon monoxide; systemic lupus erythematosus; therapy