CNRS. France: By studying the mode of action of the interl
eukin-33 protein, an al
armin for white blood
cells, a team at the Institut de Pharmaco
logie et de Biologie
Structurale (IPBS -
CNRS/Université Toulouse III - Paul Sabatier) h
as been able to evidence truncated forms of
the protein that act as potent
activators of the cells responsible for triggering allergic
reactions. This breakthrough in the understanding
of the mechanisms underlying allergy
could have important applications in the tr
eatment of asthma and other allergic diseases
such as eczema and allergic rhinitis. Co-direct
ed by CNRS researcher Corinne Cayrol and
INSERM senior researcher Jean-Philippe Gi
rard, this work is published in
PNAS
on 13
October 2014.
Interleukin-33 (IL-33), discovered in 2003 by Jean-Philippe Girard's team, is a protein in the family of
interleukins, soluble messengers that enable communication between cells
in the immune system and play
a crucial role in tissue inflammation.
This protein, which is stored in the blood vessels, lungs, skin or
intestine, is only released in the event of cell damage. It acts as an alarmin that warns the body of trauma
or infection by stimulating numerous cells in the immune system.
For several years, researchers have been trying to
understand how the activity of interleukin-33 is
regulated. They have now discovered that the protein
is released by damaged cells and is then truncated
by enzymes secreted by mastocytes, white blood cells that are key factors in allergy. By amplifying the
danger signal to the immune system, th
ese truncated forms have been shown to be 30 times more potent
than the original form of interleukin-33.
The scientists have demonstrated that this highly potent signal is able to alert cells related to lymphocytes,
group 2 innate lymphoid cells (ILC2). By triggering the chain reactions responsible for the allergic
symptoms of asthma, eczema or allergic rhinitis, these cells have an essential role in allergy.
For the research team, preventing production of the trunca
ted forms of interleukin-33 in order to reduce the
allergic reactions triggered by ILC2 represents a promising strategy for the treatment of asthma and other
allergic diseases.
This work notably received funding from the French National Research Agency (ANR), the Fondation ARC
for cancer research and the French Medical Research Foundation (Fondation pour la Recherche Médicale
- FRM)