Heme oxygenase-1-mediated CD4+CD25high regulatory T cells suppress allergic airway inflammation.
Heme oxygenase-1 (HO-1) has anti-inflammatory effects in asthma. CD4+CD25(high) regulatory T cells (Treg) are a potent immunoregulator that suppresses the immune response. We studied the effects of HO-1-mediated CD4+CD25(high) Treg on suppression of allergic airway inflammation by comparing mice treated with hemin, OVA, Sn-protoporphyrin (SnPP), and hemin plus SnPP. Airway responsiveness, airway eosinophil infiltration, the level of OVA-specific IgE, and the numbers of cells in general and eosinophils in particular in bronchial alveolar lavage fluid were lower in the hemin group than in the OVA, SnPP, and hemin plus SnPP groups. The expressions of HO-1 mRNA and protein in the lung were increased by repeated administrations of hemin and SnPP. However, the activity of HO-1 was highest in hemin mice. The percentage and suppressive function of CD4+CD25(high) Treg and the expression of Foxp3 mRNA were obviously enhanced after treatment with hemin. This increase was diminished by the administration of SnPP. The concentration of serum IL-10 was higher in the hemin group than in the other groups, whereas the level of serum TGF-beta did not significantly differ across groups. Furthermore, the ratio of IFN-gamma/IL-4 mRNA in the lung was higher in hemin-treated mice than in OVA and SnPP mice. The suppressive capacity of CD4+CD25(high) Treg was not enhanced in the IL-10-deficient mice treated with hemin. In conclusion, our experiments in the animal model demonstrated that HO-1 has anti-inflammatory effects, probably via enhancement of the secretion of IL-10 and promotion of the percentage of CD4+CD25(high) Treg.
Xia
Zhen-Wei
ZW
Department of Pediatrics, Ruijin Hospital, Medical School, Shanghai Jiaotong University, Ruijin 2nd Road 197, Shanghai 300 025, China. xzw63@hotmail.com
Zhong
Wen-Wei
WW
Xu
Li-Qing
LQ
Sun
Jian-Le
JL
Shen
Qing-Xiang
QX
Wang
Ji-Guang
JG
Shao
Jie
J
Li
Yun-Zhu
YZ
Yu
Shan-Chang
SC
D000818:Animals; D001249:Asthma / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D015704:CD4 Antigens / Q000032:analysis; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006427:Hemin / Q000276:immunology; D006967:Hypersensitivity / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D007073:Immunoglobulin E / Q000097:blood; D007249:Inflammation / Q000201:enzymology / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics; D053645:Interleukin-2 Receptor alpha Subunit / Q000037:antagonists & inhibitors; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000201:enzymology / Q000276:immunology; D008665:Metalloporphyrins / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D011524:Protoporphyrins / Q000494:pharmacology; D050378:T-Lymphocytes, Regulatory / Q000201:enzymology* / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000097:blood
D015704:CD4 Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D008665:Metalloporphyrins; D011524:Protoporphyrins; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D015847:Interleukin-4; D007073:Immunoglobulin E; D006427:Hemin; D007371:Interferon-gamma; D010047:Ovalbumin; C032628:tin protoporphyrin IX; D051547:Heme Oxygenase-1