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Researchers at ULg have discovered a subtype of eosinophil that plays a protective and beneficial role
The so-called “resident eosinophils” maintain the balance of the immune system and prevent it from responding in an abnormal way such as observed during an asthma attack. The discovery of these specific eosinophils offers promising therapeutic and prophylactic opportunities for the treatment and prevention of asthma (Data published in The Journal of Clinical Investigation).
A team of scientists directed by Professor Fabrice Bureau and Dr. Thomas Marichal, researchers at ULg’s GIGA research centre, discovered this subtype of eosinophil in mice and subsequently in humans. In mice, the nucleus of these resident eosinophils appears as a ring shape (or doughnut shape), which makes them easily distinguishable from the other inflammatory eosinophils. In humans, all eosinophils have the same morphology, which could explain why the subtypes have only just been discovered. The researchers have also demonstrated, in both mice and humans, that the resident eosinophils carry an identical marker on their surface, the protein CD62L, which means that they are easily distinguishable from inflammatory eosinophils.
By pursuing their investigations, the researchers observed that, in mice that are deficient in lung-resident eosinophils, the “allergic” immune response was greatly exacerbated after inhalation of small doses of allergens, suggesting that these specific eosinophils play a role in the prevention of asthma sensitization and therefore in the regulation of pulmonary immune homeostasis. Specifically, resident eosinophils act upstream of the inflammatory cascade by inhibiting the activation of dendritic cells. In the case of asthma as in the case of other inflammatory diseases characterized by an abnormal response of the immune system, the dendritic cells – veritable sentinels of the immune surveillance system – are activated and trigger a chain of events which ultimately results in exaggerated inflammation and clinical manifestations of the disease, which is partly due to the activation of inflammatory eosinophils.
“For the first time, this study identifies a distinct subtype of non-inflammatory pulmonary eosinophils in mice and humans which seem to be able to prevent the development of abnormal immune responses. Because these disorders of the immune system are involved in many disease conditions such as asthma, food allergies, Crohn’s intestinal disease or autoimmune diseases, this fundamental discovery is of outstanding interest to identify a way to prevent the development of these diseases”, explains Dr. Thomas Marichal.
“Recent anti-asthmatic treatments by injection of interleukin-5 monoclonal antibodies have proven to be clinically effective, but it was not understood why they did not totally eradicate the eosinophils, whose survival and function depend on interleukine-5. In light of our study, we now understand that, in fact, they spared the “good” regulating lung-resident eosinophils that are not so dependent on interleukin-5 and that is a very good thing!”, explains Professor Fabrice Bureau.
“In the future, the question is to know how to facilitate the production of resident eosinophils, rather than inflammatory eosinophils, in the bone marrow. Indeed, by acting at the top of the cascade, we will have new weapons for the prevention of inflammatory diseases such as allergies or autoimmune diseases”, concludes Professor Fabrice Bureau.
In collaboration with a team at the University of California at Los Angeles (UCLA), researchers from GIGA-Neurosciences have discovered a new gene responsible for a seizure syndrome called juvenile myoclonic epilepsy (JME). This discovery was made as part of an international consortium that studies genetic abnormalities responsible for epileptic diseases. It is being published this week in
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