Pioneering research points to a new class of targets for cancer and immune diseases

15 September 2016

The figure depicts rings of epithelial structures in the human colon interspersed with large numbers of gamma delta T cells (bright red). The current study shows that the capacity of gamma delta T cells take up residence in the gut depends upon hitherto poorly understood Butyrophilin-like molecules expressed by the epithelial cells.

Image: The figure depicts rings of epithelial structures in the human colon interspersed with large numbers of gamma delta T cells (bright red).

It's well known that the epithelial cells that line the surface of our skin and our gut provide physical and chemical barriers against dirt and pathogens. What's less well known is that they also provide a home to complex immune cell compartments that carry out tissue-based immune surveillance - like a guard providing security at a particular location versus a policeman on patrol.

By creating this home for immune cells, the epithelial cells help protect against cancer-causing agents - although it's not yet known how.

To uncover this, Adrian Hayday of the Francis Crick Institute and King's College London says: "We need to know how such tissue-resident immune cells sense the status of the body surface in which they sit. How do the cells know when things are not normal and that they need to respond?  And how do they know what responses to make?  Answering these questions could provide major clues to how the immune system monitors cancer and contributes to skin and gut inflammation.

"One key to answering these questions is to identify the molecules that body surfaces use to engage their local immune cell compartments. Once we know their identities we can ask how those molecules are altered under different conditions, such as in response to the early stages of tumour development, infection or inflammation. This knowledge might enable us to enhance the system, in the case of cancer, or to suppress the system, in the case of inflammatory diseases such as colitis or dermatitis."

In this vein, a team led by Professor Hayday has now published groundbreaking work identifying the molecules that epithelial cells use to provide this local tissue immune surveillance. Called butyrophilin-like molecules, they are poorly understood but have occasionally been implicated in cancer and inflammatory diseases. Professor Hayday's work casts a whole new light on them and provides a brand new target for cancer and inflammatory diseases.

Professor Hayday says: "By pointing the finger at butyrophilin-like molecules as the proteins that body surfaces use to regulate local T cell compartments, this work opens up new diagnostic and therapeutic possibilities. 

"Importantly, we found that this biological system holds true in mouse models and in humans, which dramatically increases the breadth of experiment options. As some of the molecules identified by this study have already been implicated in inflammatory diseases, these clues may be swiftly followed up by connecting with major clinical cohorts provided by the hospitals affiliated to King's College London."

The paper, 'Epithelia use Butyrophilin-like molecules to shape organ-specific γδ T cell compartments', is published in Cell.

  • Led by the Francis Crick Institute, scientists have identified so-called butyrophilin-like molecules that enable localised immune responses to be carried out in our body tissues. These molecules have previously been implicated in cancer and inflammatory diseases and point at a new way to tackle these conditions.
  • The work focuses on T cell compartments which are found in the epithelial cells that line our body surfaces.  Butyrophilin-like molecules play a role in shaping these compartments, allowing them to mount localised immune responses when they sense something is amiss.
  • This Crick-funded research received additional support from Cancer Research UK and the Wellcome Trust. The Crick scientists worked with colleagues at King's College London, Guy's and St Thomas' Foundation Trust in London, the Pasteur Institute in Paris, France and the University of Marburg in Germany.