Our immune system's most important function is to monitor the body
for danger signals. A classical danger signal is DNA from
micro-organisms and damaged or dying cells.
When DNA accumulates within
the cytoplasm of cells (cytoplasm comprises the entire contents of the
cell except for the cell nucleus), they will react by making interferon,
a type of signalling protein that alarms neighboring immune cells
about approaching danger.
‘A protein called IFI16, which most of our immune cells carry, has crucial significance for the cell's defense against microorganisms or dying cells' release of DNA.’
Thus far, researchers have fought to explain
these events in details. New Danish research has now taken an important
step towards doing just this.
Researchers from Aarhus University have found an important piece of
the puzzle leading towards an understanding of how our innate immune
system reacts against viral infections and recognizes foreign DNA, for
example from dying cancer cells.
The discovery may prove to be of great
importance for immunological treatment of cancer as well as autoimmune
diseases in the future.
"We have discovered that a protein called IFI16, which most of our
immune cells carry, has crucial significance for the cell's defense
against microorganisms or dying cells' release of DNA," explains one of
the researchers behind the study, Associate Professor Martin Roelsgaard
Jakobsen from the Department of Biomedicine, Aarhus University, about
the results, which have just been published in Nature Communications
Knowledge about how IFI16 works in immune cells and how it helps to
initiate and control an immune response can have major long term
potential for various types of immunotherapies that are used in the
treatment of cancer.
Examined cellular debris
The innate immune system consists of many different knobs that
can be 'pulled' to fight infections by initiating the production of
interferon and various inflammatory cytokines. One of these knobs is
called STING, a protein that is activated when immune cells sense the
presence of DNA parts outside the cell nucleus.
"STING's function and its degree of activity play a significant role
in how well the body fights conditions when it is exposed to something
that is foreign or abnormal such as infections and cancer," explains
Martin Roelsgaard Jakobsen.
In the new study, the researchers chose to investigate the function
of STING in one of the most essential immune cells known to engulf
cell-free DNA - the macrophages. They deleted different genes from
macrophages' genetic backbone and examined whether the "STING knob"
continued to function. It turned out that when the gene which encodes
the protein IFI16 was depleted, macrophages stopped producing an immune
response and halted production of interferon when exposed to cell-free
DNA or DNA viruses.
"By using different molecular biological methods, we could clearly
demonstrate that our immune cells only need a very small fraction of the
IFI16 protein for STING to function optimally," says Martin Roelsgaard
The researchers are currently making use of the new knowledge to
develop ways in which they can turn the STING knob in different
directions - either up or down in the activity - with the help of
synthetic designed molecules.
"Within the next five to seven years we hope to have developed a new
form of medicine that can support current immunotherapies in the cancer
field, where we go directly in and boost the innate immune defence
system in the cancerous tumor by using molecules that targets and
triggers STING and IFI16 function," explains Martin Roelsgaard Jakobsen.