title: Human mesenchymal stem cells elevate CD4+CD25+CD127low/- regulatory T cells of asthmatic patients via heme oxygenase-1.
abstract: Up-regulation of CD4+CD25+CD127low/- regulatory T cells (Tregs) is a new target in the treatment of asthma. Human bone marrow mesenchymal stem cells can up-regulate CD4+CD25+CD127low/- regulatory T cells in vitro, meanwhile, heme oxygenase-1 (HO-1) plays an important role in the development and maintenance of CD4+CD25+ regulatory T cells. However the mechanism has not yet been adequately understood. Hence, we wondered what effect of Heme Oxygenase-1 made on regulation of CD4+CD25+CD127low/- regulatory T cells mediated by mesenchymal stem cells. Peripheral blood mononuclear cells isolated from asthmatic patients and healthy controls were co-cultured with human bone marrow mesenchymal stem cells which were pretreated with Hemin (the revulsive of Heme Oxygenase-1), Protoporphyrin Ⅸ zinc (the inhibitor of Heme Oxygenase-1) and saline. The expression of Heme Oxygenase-1 in MSCs was enhanced by Hemin and inhibited by Protoporphyrin  zinc in vitro. Overexpression of Heme Oxygenase-1 elevated the proportion of CD4+CD25+CD127low/- regulatory T cells in CD4+ T cells, meanwhile, inhibition of Heme Oxygenase-1 decreased the proportion of CD4+CD25+CD127low/- regulatory T cells in CD4+ T cells as compared with mesenchymal stem cells alone. Taken together, these data demonstrated that Heme Oxygenase-1 contributed to the up-regulation of CD4+CD25+CD127low/- regulatory T cells mediated by mesenchymal stem cells in asthma.
authors.affiliation: Department of Respirology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Respiratory Disease Research Institute of Sun Yat-Sen University, Guangzhou, Guangdong province, People's Republic of China. jgli88@126.com.
authors.forename: Jian-guo
authors.initials: JG
authors.lastname: Li
authors.forename: Yong-xun
authors.initials: YX
authors.lastname: Zhuan-sun
authors.forename: Bing
authors.initials: B
authors.lastname: Wen
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.forename: Feng-ting
authors.initials: FT
authors.lastname: Huang
authors.forename: Hridaya bibhu
authors.initials: Hb
authors.lastname: Ghimire
authors.forename: Pi-xin
authors.initials: PX
authors.lastname: Ran
mesh_terms: D001249:Asthma / Q000276:immunology*; D002478:Cells, Cultured; D051858:Forkhead Transcription Factors / Q000502:physiology; D051547:Heme Oxygenase-1 / Q000502:physiology*; D006427:Hemin / Q000494:pharmacology; D006801:Humans; D053699:Interleukin-7 Receptor alpha Subunit / Q000032:analysis*; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D011524:Protoporphyrins / Q000494:pharmacology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053699:Interleukin-7 Receptor alpha Subunit; D011524:Protoporphyrins; C017803:zinc protoporphyrin; D006427:Hemin; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1