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Transcriptional and functional defects of dendritic cells derived from the MUTZ‐3 leukaemia line
Author(s) -
Rasaiyaah Jane,
Noursadeghi Mahdad,
Kellam Paul,
Chain Benjamin
Publication year - 2009
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2008.03018.x
Subject(s) - biology , cd14 , microbiology and biotechnology , chemokine , phenotype , cell culture , dendritic cell , transcriptome , population , myeloid , cancer research , antigen , gene , immunology , immune system , gene expression , genetics , medicine , environmental health
Summary Dendritic cells (DC) generated from MUTZ‐3, an immortalized acute myeloid leukaemia‐derived cell line, have potential application as a model for the study of human DC, and as a tool with which to stimulate immunotherapeutic responses to cancer. However, the relationship of MUTZ‐3 DC to their non‐transformed counterparts remains incompletely understood. Immunoselected CD14 + MUTZ‐3 cells were used to generate a homogeneous population of DC (M3DC). These cells had a cell surface phentoype and morphology characteristic of conventional monocyte‐derived DC (MDDC). Whole genome transcriptome comparison of M3DC and MDDC however, revealed extensive differences between these two cell types. Functional ontology‐based data analysis revealed three enriched clusters of genes downregulated in M3DC, with functions in pathogen recognition, DC maturation and cytokine/chemokine signalling. Downregulation of protein expression was confirmed for several of these genes. The molecular differences were accompanied by a profoundly impaired phenotypic and functional response of M3DC to microbial stimulation. The immortalized phenotype of MUTZ‐3 therefore reflects not only deregulated proliferative capacity, but substantial perturbation of normal antigen‐presenting cell function. These results have important implications for studies using MUTZ‐3 as a model of MDDC or for cancer immunotherapy.