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Carbon monoxide exposure improves immune function in lupus‐prone mice
Author(s) -
MackernOberti Juan P.,
Llanos Carolina,
Carreño Leandro J.,
Riquelme Sebastián A.,
Jacobelli Sergio H.,
Anegon Ignacio,
Kalergis Alexis M.
Publication year - 2013
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12124
Subject(s) - autoimmunity , immune system , heme oxygenase , immunology , systemic lupus erythematosus , biliverdin , autoimmune disease , pathogenesis , medicine , heme , biology , antibody , chemistry , disease , enzyme , biochemistry
Summary S ystemic lupus erythematosus ( SLE ) is an autoimmune disease characterized by multiple alterations affecting the normal function of immune cells, such as lymphocytes, dendritic cells ( DC s) 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 F e 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 DC s, we evaluated whether induction of HO ‐1 expression or the administration of CO could ameliorate disease in the F cγ RII b knockout ( KO ) mouse model for SLE . We found that CO administration decreased the expansion of CD 11b + cells, prevented the decline of regulatory T cells and reduced anti‐histone antibodies observed in untreated F cγ RII b 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 F cγ RII b KO mice, highlighting HO ‐1 as a potential new target for autoimmune therapy.