Pivotal Advance: Heme oxygenase 1 expression by human CD4+ T cells is not sufficient for their development of immunoregulatory capacity.
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(+) T(regs) and induced in CD4(+)CD25(-) T cells upon FoxP3 transfection. Here, we investigated whether HO-1 was essential and sufficient for human T(regs) to exert immunosuppression in vitro. PGJ(2) induced pronounced expression of HO-1 in CD4(+)CD25(-) T cells without accompanying FoxP3 induction. Treatment of CD4(+)CD25(-) T cells with PGJ(2) decreased their proliferation, whereas the HO-1 inhibitor SnPP enhanced the proliferation of HO-1-expressing T(regs), suggesting that HO-1 may modulate the proliferative capacity of T lymphocytes. HO-1 modulation by SnPP treatment of T(regs) or PGJ(2) 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 T(regs) might contribute to their typical reluctance to proliferate but does not account independently for their suppressive functions.
Nikolaus Fiebiger Center for Molecular Medicine, Medical Department III, University Hospital of Erlangen, Germany.
Markus
M
Biburger
Gabi
G
Theiner
Mirjam
M
Schädle
Gerold
G
Schuler
Gisa
G
Tiegs
D000970:Antineoplastic Agents / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051858:Forkhead Transcription Factors / Q000276:immunology / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology*; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects / Q000502:physiology*; D007376:Interleukin-2 / Q000096:biosynthesis / Q000276:immunology; D008665:Metalloporphyrins / Q000494:pharmacology; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000494:pharmacology; D011524:Protoporphyrins / Q000494:pharmacology; D050378:T-Lymphocytes, Regulatory / Q000201:enzymology* / Q000276:immunology
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508594:IL2 protein, human; D007376:Interleukin-2; D008665:Metalloporphyrins; D011524:Protoporphyrins; C037112:9-deoxy-delta-9-prostaglandin D2; C032628:tin protoporphyrin IX; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D015230:Prostaglandin D2