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 ?? T cell compartments', is published inCell.