title: Thymosin-alpha1 modulates dendritic cell differentiation and functional maturation from human peripheral blood CD14+ monocytes.
abstract: Although thymosins have been demonstrated to have immunomodulatory effects, it is still not clear whether they could affect dendritic cells (DCs), the most professional antigen-presenting cells. The objective of this study was to determine the effect and potential mechanisms of thymosin-alpha1 (Talpha1) on DC differentiation and functional maturation. Human peripheral blood CD14(+) monocytes were purified by using a magnetic separation column and cultured with GM-CSF and IL-4 to differentiate into immature DCs (iDCs). In the presence of Talpha1, iDC surface markers CD40, CD80, MHC class I and class II molecules were significantly upregulated as measured by flow cytemotry analysis. However, Tbeta4 or Tbeta10 did not show these effects on iDCs. There was an approximately 30% reduction in antigen (FITC-conjugated dextran)-uptake by Talpha1-treated iDCs as compared with non-Talpha1-treated iDCs. In addition, Talpha1-treated matured DCs (mDCs) showed an increased stimulation of allogeneic CD3(+) T-cell proliferation as measured by a mixed-lymphocyte reaction assay. Talpha1-treated mDCs also increased the production of several Th1- and Th2-type cytokines as measured by a Bio-Plex cytokine assay. Furthermore, rapid activation of p38 MAPK and NFkappaB was seen in Talpha1-treated iDCs as measured by a Bio-Plex phosphoprotein assay. Thus, Talpha1 significantly enhances DC differentiation, activation, and functions from human peripheral blood CD14(+) monocytes possibly through a mechanism of the activation of p38 MAPK and NFkappaB pathways. This study provides a basis to further evaluate Talpha1 as a possible adjuvant for a DC-directed vaccine or therapy.
authors.affiliation: Molecular Surgeon Research Center, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. qizhiyao@bcm.edu <qizhiyao@bcm.edu>
authors.forename: Qizhi
authors.initials: Q
authors.lastname: Yao
authors.forename: Linh X
authors.initials: LX
authors.lastname: Doan
authors.forename: Rongxin
authors.initials: R
authors.lastname: Zhang
authors.forename: Uddalak
authors.initials: U
authors.lastname: Bharadwaj
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.forename: Changyi
authors.initials: C
authors.lastname: Chen
mesh_terms: D000276:Adjuvants, Immunologic; D002454:Cell Differentiation; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000097:blood / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D009000:Monocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D000077596:Thymalfasin; D013947:Thymosin / Q000031:analogs & derivatives* / Q000276:immunology / Q000378:metabolism; D000099201:Thymosin beta(4)
chemical_list: D000276:Adjuvants, Immunologic; D016207:Cytokines; D018950:Lipopolysaccharide Receptors; D000077596:Thymalfasin; D013947:Thymosin; D000099201:Thymosin beta(4); C039302:thymosin beta(10)