title: Hypoxia skews dendritic cells to a T helper type 2-stimulating phenotype and promotes tumour cell migration by dendritic cell-derived osteopontin.
abstract: It is well recognized that tissue microenvironments are involved in regulating the development and function of dendritic cells (DC). Oxygen supply, which varies in different tissues, has been accepted as an important microenvironmental factor in regulating the biological functions of several immune cells and as being involved in tumour progression and metastasis. However, little is known about the effect of hypoxia on the biological functions of DC and the effect of these hypoxia-conditioned DC on tumour metastasis. In this study, we analysed the transcriptional profiles of human monocyte-derived immature DC (imDC) and mature DC (mDC) cultured under normoxia and hypoxia by microarray, and found a body of potential targets regulating the functions of DC during hypoxia. In addition, the phagocytic ability of hypoxic imDC markedly decreased compared with that of normoxic imDC. Importantly, hypoxic DC poorly induced the proliferation of allogeneic T cells, but polarized allogeneic CD4(+) naive T cells into a T helper type 2 (Th2) response. Moreover, hypoxic DC secreted large amounts of osteopontin, which were responsible for the enhanced migration of tumour cells. Therefore, our study provides new insights into the biological functions of DC under hypoxic conditions and one of mechanisms underlying tumour immune escape during hypoxia.
authors.affiliation: Institute of Basic Medical Sciences, Qilu Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Meixiang
authors.initials: M
authors.lastname: Yang
authors.forename: Chunhong
authors.initials: C
authors.lastname: Ma
authors.forename: Shuxun
authors.initials: S
authors.lastname: Liu
authors.forename: Jintang
authors.initials: J
authors.lastname: Sun
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Shao
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Gao
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Zewu
authors.initials: Z
authors.lastname: Li
authors.forename: Qi
authors.initials: Q
authors.lastname: Xie
authors.forename: Zhaogang
authors.initials: Z
authors.lastname: Dong
authors.forename: Xun
authors.initials: X
authors.lastname: Qu
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D000860:Hypoxia / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology; D053495:Osteopontin / Q000378:metabolism*; D010587:Phagocytosis / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D019139:Tumor Escape; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
chemical_list: D016207:Cytokines; D053495:Osteopontin