title: Novel immunostimulators with a thiazolidin-4-one ring promote the immunostimulatory effect of human iNKT cells on the stimulation of Th2-like immune responsiveness via GATA3 activation in vitro.
abstract: Invariant natural killer T cells (iNKTs) are important innate immune cells which get involved in various immune responses in both mice and humans. These immune reactions range from self-tolerance to development of autoimmunity and responses to pathogens and tumor development. In this study, we aimed to explore the effects of the novel immunostimulators (CH1b and CH2b) containing thiazolidin-4-one on the functions of human invariant natural killer T cells (iNKTs). First of all, iNKTs in peripheral blood mononuclear cells were expanded with α-Galactosylceramide (α-Galcer) in vitro. Then, the highly purified iNKTs were isolated from PBMCs using magnetic cells sorting (MACS). Next, we investigated the impacts of CH1b and CH2b on proliferation, cytokines production, cytotoxicity, and the associated signaling pathways in iNKT cells. Finally, we found that CH2b could significantly promote the activated iNKTs proliferation, increase the production of Th2 cytokines, and induce Th0 differentiation into Th2 subset via GATA 3 signaling pathway. Besides, CH2b could markedly enhance the cytotoxic ability of the activated iNKTs. Therefore, we concluded that CH2b, a promising candidate immunostimulator, might be used for the treatment of infections, tumors, autoimmune and allergic diseases, and for the correction of Th1/Th2 balance disorders in future.
authors.affiliation: Department of Immunology, School of Medicine, Hebei University, Baoding 071000, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Meng
authors.affiliation: Department of Immunology, School of Medicine, Hebei University, Baoding 071000, China.
authors.forename: Chunxiao
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Immunology, School of Medicine, Hebei University, Baoding 071000, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Yang
authors.affiliation: Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry & Environmental Science, Hebei University, Baoding 071002, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Chen
authors.affiliation: Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry & Environmental Science, Hebei University, Baoding 071002, China.
authors.forename: Xiaoliu
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Immunology, School of Medicine, Hebei University, Baoding 071000, China.
authors.forename: Yongbin
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Immunology, School of Medicine, Hebei University, Baoding 071000, China. Electronic address: chenddzz@163.com.
authors.forename: Dongzhi
authors.initials: D
authors.lastname: Chen
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D050990:GATA3 Transcription Factor / Q000378:metabolism*; D005699:Galactosylceramides / Q000276:immunology; D006801:Humans; D007114:Immunization; D008213:Lymphocyte Activation / Q000187:drug effects; D055611:Natural Killer T-Cells / Q000187:drug effects* / Q000276:immunology; D009705:Nucleosides / Q000138:chemical synthesis / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D018418:Th2 Cells / Q000276:immunology; D053778:Thiazolidines / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: C000617124:CH1b compound; C000617125:CH2b compound; D016207:Cytokines; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D005699:Galactosylceramides; D009705:Nucleosides; D053778:Thiazolidines; C493154:alpha-galactosylceramide
keywords: IFN-γ/IL-4; Immunostimulators; Invariant natural killer T cells; α-Galcer