Three-dimensional synthetic cells have revealed the hidden messages of the immune system.
Research led by Professor Mike Dustin’s group of the Kennedy Institute of Rheumatology at the University of Oxford has tracked the movement of ectosomes and unravelled their contents.
As described in their research findings, published in eLIFE, the team developed a three-dimensional synthetic cell and successfully intercepted and deciphered the messages contained in helper T cell derived ectosomes – which play an important role in the immune system.
Super resolution microscopy
By employing super resolution microscopy, called dSTORM, the research found that T cell synaptic ectosomes have size scales of a millionth of a meter but despite their reduced size they can package enough information to orchestrate the response of dendritic cells.
In addition, cell free ectosomes and their synthetically engineered versions result in dendritic cell maturation, an essential process for the establishment of adequate immune system responses.
Finally, by employing mass spectrometry and CRISPR-Cas9 gene editing technology, the team further explained the key molecular machinery, known as ESCRT proteins, responsible for the dispatch of ectosomes from helper T cells.
Co-lead author of the study Dr. David Saliba said: “This research revealed that the formation and composition of these ectosomes depends on direct molecular interactions at the immune synapse and has profound implications on understanding cell-to-cell communication.
“Harnessing this new knowledge is important for the development of future therapies that can help shape the immune response to specific diseases.”
How immune cells work
Immune cells mobilise and coordinate a competent defence response when they detect harmful pathogens or cancer. In order to do this it is vital that the cells communicate in a way that is tailored to the pathogenic insult. Consequently, the body’s response to various health challenges depends on successful coordination among the cells of the immune system.
Key players of the immune system include helper T cells and antigen presenting cells, such as dendritic cells and the antibody-producing B cells. Through short-lived contacts called immune synapses T cells communicate with antigen presenting cells which are highly specialised endowing cells with the appropriate platform for exchanging information in a timely and efficient manner. Key messages are dispatched across the immune synapse via nanometer size vesicles referred to as synaptic ectosomes.