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Molecular and functional characterisation of dendritic cells derived from the MUTZ-3 acute myeloid leukaemia

Rasaiyaah, J.T.; (2009) Molecular and functional characterisation of dendritic cells derived from the MUTZ-3 acute myeloid leukaemia. Doctoral thesis, UCL (University College London).

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Abstract

Dendritic Cells (DC) are a group of professional antigen presenting cells that act as sentinels for the body's defense system against microbial pathogens. DC respond to local signals from invading pathogens, by migrating to lymph nodes or spleen, and there activating T-cell dependent antigen-specific immune responses. Both quantitative and qualitative parameters of the immune response depend critically on signals given out by DC. These signals, in turn, depend on complex signal transduction pathways triggered in the DC by exposure to different types of microbes. These pathways are engaged by pattern recognition receptors such as Toll-like receptors (TLRs) and various sugar-binding receptors. The integration of DC signalling pathways, and how this controls the eventual type of T cell response remains a central question of immunology. The thesis focuses on the characterisation of the MUTZ-3 cell line as a DC model. The MUTZ-3 acute myeloid leukaemia cell line has previously been proposed as a useful in vitro model for DC. The cell line is not homogenous and contains a mixture of different differentiation stages. The first results chapter focuses on optimisation of DC differentiation and purification in this model, as well as the activation using different TLRs. The second focuses on the analysis and validation of base line array data comparing the MUTZ-3 cells to DC. Gene expression analysis revealed differences between M3DC and MDDC, amounting to over 5% of the transcriptome. The differentially expressed genes were enriched with functional cluster representing cellular responses to external stimuli. The role of mixed linage kinases (MLK) in DC signalling forms the final results chapter. It has been observed that a small molecular weight inhibitor of MLK blocks DC maturation in response to some ligands but not others. MLK may therefore be an interesting surrogate for DC activation. This chapter investigates the role of MLKs in MUTZ-3 using protein inhibitors, RNAi and dominant negative mutants.

Type:Thesis (Doctoral)
Title:Molecular and functional characterisation of dendritic cells derived from the MUTZ-3 acute myeloid leukaemia
Language:English
Additional information:Authorisation for digitisation not received
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Infection and Immunity (Division of) > Research Department of Infection

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