With Wnt4, it will now be possible to combat age-related
decline in immune response, thanks to the work of Dr. Claude Perreault and his
team of researchers at the Institute for Research in Immunology and Cancer
(IRIC) at the Université de Montreal in Canada
and the University of Oulu in Finland.
One of the most obvious signs of the age-related decline of
the immune system is the atrophy of the thymus, a small gland at the base of
the neck where T cells mature. This decline becomes significant towards the age
of 50. It is caused not only by a decreased output of T cells from the thymus,
but also by a decreased ability to recognize new antigens. The result is an
increased susceptibility to infection as well as a lowered resistance to the
immunosuppressive effects of chemotherapy.
"Thymic atrophy is a major public health problem. It
compromises the efficacy of vaccination and weakens the resistance to common
viruses, for instance to the respiratory syncytial virus (RSV), which is
responsible each year for the hospitalization of more than 150,000 people in
This is due to the fact that ''old'' T cells are not equipped to face the
threat of new foreign bodies, whether they are viruses or tumours," said
The researchers induced overproduction of the Wnt4 protein
in the cells of the mouse immune system and saw the stimulatory effect this
protein exerts on the development of white blood cells.
By using molecular markers that are specific to the
different stages of cell maturation, the researchers determined that elevated
levels of Wnt4 led to a marked increase in the number of white blood cell
progenitors, and of immature T cells in the thymus in particular.
On the other hand, they found that deletion of the Wnt4 gene
and lack of the corresponding protein was linked with a decrease in the number
of T cell progenitors in the thymus.
After showing that Wnt4 could stimulate thymopoiesis, the
name given to the production of T cells in the thymus, researchers wanted to
understand the mode of action of the protein.
Isabelle Louis, a graduate student, and Dr. Krista Heinonen,
a postdoctoral fellow, analyzed the changes in gene activity triggered by
exposure to Wnt4 and found that the results were conclusive: Wnt4 increases the number of T cell
progenitors by inducing the expression of genes involved in cell survival.
IRIC researchers also showed that Wnt4 does not mediate
these changes in gene expression through the intracellular pathway normally
activated by members of the Wnt family, i.e. stabilization of a signalling
protein called -catenin, but rather through an alternative pathway involving
members of the JNK family of proteins.
Now the researchers are investigating ways to capitalize on
its discovery to develop new therapeutic agents.
The study is published in the latest edition of the journal