title: Heme Oxygenase-1-Expressing Dendritic Cells Promote Foxp3+ Regulatory T Cell Differentiation and Induce Less Severe Airway Inflammation in Murine Models.
abstract: Dendritic cells (DCs) are critical for instructing immune responses toward inflammatory or anti-inflammatory status. Heme oxygenase-1 (HO-1) is known for its cytoprotective effect against oxidative stress and inflammation, suggesting its immune regulatory role in allergic lung inflammation. HO-1 has been implicated in affecting DC maturation; however, its role in DC-mediated T-cell differentiation is unclear. In this study, we demonstrated that HO-1-expressing bone marrow-derived dendritic cells (BM-DCs) displayed tolerogenic phenotypes, including their resistance to lipopolysaccharide (LPS)-induced maturation, high level expression of IL-10, and low T-cell stimulatory activity. In addition, HO-1-expressing DCs were able to induce antigen-specific Foxp3+ regulatory T cells (Treg) differentiation in vitro and in vivo. Also, HO-1-expressing DCs modulated the severity of lung inflammatory responses in two murine models of airway inflammation. This study provided evidence supporting the role of HO-1-expressing DCs in tolerance induction and as a potential therapeutic target for allergic asthma as well as other inflammatory diseases.
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Tzu-Hsuan
authors.initials: TH
authors.lastname: Wong
authors.affiliation: Department of Allergy-Immunology-Rheumatology, Chi-Mei Medical Center, Tainan, Taiwan.
authors.forename: Hung-An
authors.initials: HA
authors.lastname: Chen
authors.affiliation: Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, Tainan, Taiwan.
authors.forename: Rung-Jiun
authors.initials: RJ
authors.lastname: Gau
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Division of Rheumatology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Jeng-Hsien
authors.initials: JH
authors.lastname: Yen
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Research Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Jau-Ling
authors.initials: JL
authors.lastname: Suen
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008665:Metalloporphyrins / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D010641:Phenotype; D011014:Pneumonia / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D008070:Lipopolysaccharides; D008665:Metalloporphyrins; D051547:Heme Oxygenase-1