Synthetic cells capture and reveal hidden messages of the immune system

When immune cells detect harmful pathogens or cancers, they mobilize and coordinate a competent defense response. To do this, the immune cells must communicate appropriately to the pathogenic insult. Therefore, the body's response to various health problems depends on a successful coordination between the cells of the immune system.

The major players in the immune system include helper T cells and antigen presenting cells, such as dendritic cells and antibody producing B cells. T cells communicate with antigen-presenting cells through ephemeral contacts called immune synapses. These contacts are highly specialized cells with the appropriate platform to exchange information quickly and efficiently. Key messages are distributed in the immune synapse via nanoscale vesicles called synaptic ectosomes.

Research conducted by Professor Mike Dustin's group at the Kennedy Institute of Rheumatology at Oxford University followed the movement of ectosomes and revealed their contents. As described in the results of his research published in eLIFE, the team developed a three-dimensional synthetic cell and successfully intercepted and deciphered the messages contained in ectosomes derived from helper T cells. Using super-resolution microscopy, called dSTORM, this work showed that these synaptic T-cell ectosomes had a scale of one millionth of a meter, but despite their small size, they could contain enough information to orchestrate the response. dendritic cells. In addition, cell free ectosomes and their synthetically modified versions result in the maturation of dendritic cells, an essential process for establishing adequate immune responses.

The dSTORM experiments have also shown how antigen recognition and effector functions can fuse into single ectosomes, which implies that the T-cell-mediated help is highly targeted. Finally, using mass spectrometry and CRISPR-Cas9 gene editing technology, the team then elucidated key molecular mechanisms, known as ESCRT proteins, responsible for sending of ectosomes from helper T cells.

"This research has revealed that the formation and composition of these ectosomes depend on direct molecular interactions at the level of the immune synapse and have profound implications for the understanding of cell-to-cell communication," said the co-author. from the study, Dr. David Saliba. Exploiting this new knowledge is important for the development of future treatments that can help shape the immune response to specific diseases.