title: Immunomodulatory function of regulatory dendritic cells induced by mesenchymal stem cells.
abstract: Mesenchymal stem cells (MSCs) provide an excellent model for development of stem cell therapeutics, and their potential treatment in the immunopathogenic diseases have gained further interest after demonstration of immunomodulatory effects on complicated interactions between T cells and even dendritic cells (DCs). However, the mechanisms underlying these immunoregulatory effects of MSCs are poorly understood. In this study, we show that bone marrow derived MSCs can differentiate mature DCs (mDCs) into a distinct regulatory DC population. Compared with mDCs, they have lower expression of CD1a, CD80, CD86 and CD40, but higher expression of CD11b. MSCs induced DCs (MSC-DCs) can hardly stimulate T-cell proliferation even when MSC-DCs are stimulated by LPS. In addition, high endocytosic capacity, low immunogenicity, and strong immunoregulatory function of MSC-DCs are also observed. Moreover, MSC-DCs can efficiently generate CD4+CD25+Foxp3+ Treg cells from CD4+CD25-Foxp3-T cells. The inhibitory function of MSC-DCs is mediated not only through TGF-β1, but also by inducing the production of Treg cells or T-cell anergy. These results demonstrate that the immunomodulatory effects of regulatory DCs induced by MSCs provide efficacious treatment for immunopathogenic diseases.
authors.affiliation: Department of Hematology and Oncology, The Oncology Hospital of Tianjin Medical University, Tianjin, PR China. zhao_dor001@yahoo.com.cn
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: Zhao
authors.forename: Wen
authors.initials: W
authors.lastname: Xu
authors.forename: Li
authors.initials: L
authors.lastname: Sun
authors.forename: Yong
authors.initials: Y
authors.lastname: You
authors.forename: Fang
authors.initials: F
authors.lastname: Li
authors.forename: Qiu-Bai
authors.initials: QB
authors.lastname: Li
authors.forename: Ping
authors.initials: P
authors.lastname: Zou
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D001853:Bone Marrow / Q000276:immunology*; D002450:Cell Communication; D002454:Cell Differentiation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D004705:Endocytosis; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D056747:Immunomodulation; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D053773:Transforming Growth Factor beta1 / Q000276:immunology; D055815:Young Adult
chemical_list: D015703:Antigens, CD; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053773:Transforming Growth Factor beta1