Pivotal Advance: Heme oxygenase 1 expression by human CD4+ T cells is not sufficient for their development of immunoregulatory capacity

Journal of Leukocyte Biology

Gabi Theiner³  Gisa Tiegs⁴  Gerold Schuler³  Mirjam Schädle²  Markus Biburger¹ 

[1] Nikolaus Fiebiger Center for Molecular Medicine, Medical Department III, and Institute of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nuremberg, Germany; and Nikolaus Fiebiger Center for Molecular Medicine, Medical Department III, and Nikolaus Fiebiger Center for Molecular Medicine, Medical Department III, and Institute of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nuremberg, Germany; and Institute of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nuremberg, Germany; and Nikolaus Fiebiger Center for Molecular Medicine, Medical Department III, and Institute of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nuremberg, Germany; and;Institute of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nuremberg, Germany; and Institute of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nuremberg, Germany; and Institute of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nuremberg, Germany; andDepartment of Dermatology, University Hospital of Erlangen, Germany; Department of Dermatology, University Hospital of Erlangen, Germany; Department of Dermatology, University Hospital of Erlangen, Germany;;Institute of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nuremberg, Germany; and Division of Experimental Immunology and Hepatology, Center of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany Institute of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nuremberg, Germany; and Institute of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nuremberg, Germany; and Division of Experimental Immunology and Hepatology, Center of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany Division of Experimental Immunology and Hepatology, Center of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany Institute of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nuremberg, Germany; and Division of Experimental Immunology and Hepatology, Center of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

关键词: tolerance;    regulatory T cells;    immune modulation;    CD4⁺CD25⁺ T_regs;    proliferation;   

DOI  :  10.1189/jlb.0508280

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

HO-1 is the only inducible one of three isoenzymes that catalyzes the oxidative degradation of heme. HO-1 is inducible by various cellular stress factors and exerts cytoprotective and immunomodulatory effects. Recent publications demonstrated that HO-1 is constitutively expressed by CD4+CD25+ Tregs and induced in CD4+CD25− T cells upon FoxP3 transfection. Here, we investigated whether HO-1 was essential and sufficient for human Tregs to exert immunosuppression in vitro. PGJ2 induced pronounced expression of HO-1 in CD4+CD25− T cells without accompanying FoxP3 induction. Treatment of CD4+CD25− T cells with PGJ2 decreased their proliferation, whereas the HO-1 inhibitor SnPP enhanced the proliferation of HO-1-expressing Tregs, suggesting that HO-1 may modulate the proliferative capacity of T lymphocytes. HO-1 modulation by SnPP treatment of Tregs or PGJ2 treatment of CD4+CD25− T cells neither suppressed nor induced immune-modulatory function in these cells, respectively, as measured by responder-cell proliferation and/or IL-2 production. In summary, these data suggest that HO-1 expression by Tregs might contribute to their typical reluctance to proliferate but does not account independently for their suppressive functions.

【 授权许可】

Unknown