Developmental control of translation during DC development
We have generated data on the developmental control of translation during DC activation. Our work (Lelouard et al., JCB) demonstrates that DCs down-regulate and change the quality of translation in order to increase their survival, however during this process MHC I antigen processing is affected. This has important consequences for the way antigens should be introduced in DCs and how long after stimulation they should be used during vaccination application.
We have also initiated studies on the impact of dsRNA on the regulation of translation and the functional response of DCs (IFN production). We have now demonstrated that DCs enters an “unfolded protein response-like state and controls the phosphorylation of a key translation initiation factor (eIF2-a). The quality of the translation is not only affected, but the overall capacity of DCs to respond to stress is also modified in order to increase their survival and resistance to viral infection. This observation has important consequences on the use of different adjuvants during DC based vaccination trial.
We are going to finalize the projects with several publications. We will follow-up our studies on the impact of dsRNA on the regulation of translation and focus on DCs in vivo and on the regulation of IFN production.
data set
preclinical study dataset
Regulation of translation is required for dendritic cell function and survival during activation.
MHC class II stabilization at the surface of human dendritic cells is the result of maturation-dependent MARCH I down-regulation.
E3-ubiquitin ligase MARCH I
Major histocompatibility complex class I
Major histocompatibility complex class II
Molecular entity
immature dendritic cell
Homo sapiens
double-stranded RNA
interferon
Philippe Pierre
development or differentiation experiment