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* Department of Genetics, Biology and Biochemistry, and Molecular Biotechnology Center;
Department of Medicine and Experimental Oncology, University of Turin, Turin, Italy;
Center for Experimental Research and Medical Studies;
Department of Internal Medicine, San Giovanni Battista Hospital, Turin, Italy; and
¶ Department of Neurobiology, Institute of Anatomy, University of Aarhus, Århus, Denmark
Several factors affect the autoimmune response, including iron-dependent modulation of T cells. Hemopexin is the plasma protein with the highest binding affinity to heme. It mediates heme-iron recovery in the liver, thus controlling heme-iron availability in peripheral cells. The aim of the present study was to investigate the role of hemopexin in the progress of an autoimmune response. To this end, we chose a mouse model of mercury-induced autoimmunity and evaluated the susceptibility of hemopexin-null mice to mercury treatment compared with wild-type controls. In this study we show that lack of hemopexin dampens mercury-induced autoimmune responses in mice. Hemopexin-null mice produced fewer antinuclear autoantibodies and had reduced deposits of immune complexes in the kidney after mercuric chloride treatment compared with wild-type mice. These features were associated with a reduction in activated T cells and lower absolute B cell number in spleen and impaired IgG1 and IgG2a production. In contrast, in hemopexin-null mice the response to OVA/CFA immunization was maintained. In addition, hemopexin-null mice had reduced transferrin receptor 1 expression in T cells, possibly due to the increase in heme-derived iron. Interestingly, CD4+T cells isolated from mercury-treated hemopexin-null mice show reduced IFN-
-dependent STAT1 phosphorylation compared with that of wild-type mice. Our data suggest that hemopexin, by controlling heme-iron availability in lymphocytes, modulates responsiveness to IFN- and, hence, autoimmune responses.
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1 This work was supported by the Italian Ministry of University and Research to E.T. and F.A., and by Regione Piemonte to F.A. and B.B. (Grant A141). C.C. is supported by a fellowship from Fondazione Denegri.
2 Address correspondence and reprint requests to Dr. Sharmila Fagoonee, University of Turin, Via Nizza 52, Turin, Italy. E-mail address: sharmila.fagoonee{at}unito.it or Dr. Benedetta Bussolati, Molecular Biotechnology Center, Via Nizza 52, 10126 Turin, Italy. E-mail address: benedetta.bussolati{at}unito.it
3 E.T. and B.B. contributed equally to this work.
4 Abbreviations used in this paper: HO, heme-oxygenase; ANA, antinuclear antibody; CO, carbon monoxide; HgCl2, mercuric chloride; Hx-null, hemopexin-null; IC, immune complex; TfR1, transferrin receptor 1; Treg, T regulatory cell.
This article has been cited by other articles:
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  M. P. Fink Editorial: Hemopexin: newest member of the anti-inflammatory mediator club J. Leukoc. Biol., August 1, 2009; 86(2): 203 - 204. [Full Text] [PDF]
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