Despite the increasing prevalence of allergies in the western world, some of their development mechanisms remain unknown. Together with his "Asthma, Allergy and Immunotherapy" research team, Laurent Reber is devoted to elucidating the role of some of their effectors – the IgE and IgG immunoglobulins. Research that is expected to open up major therapeutic avenues…
You are a trained chemist. What led you to work in biology?
Indeed, I started by studying chemistry and biochemistry, with the aim of getting into drug development. But I gradually began to discover the fields of physiology and immunology, giving me an insight into the mechanisms of disease. Biology also became a key focus, with my senior professional diploma being in chemistry and biology. My thesis constituted my first plunge into the allergy field because it was devoted to the inflammatory mechanism related to certain lung diseases and more particularly to a key cell: the mastocyte. Immunology then formed the core of my postdoctoral research and the start of my career as a researcher at Stanford University, which is where I developed animal models for the study of such pathophysiological mechanisms as anaphylactic shock. And since I joined Inserm in 2016, my chemistry background has been useful to the pharmacological research approaches that we are developing.
Your research is centered around allergic mechanisms. Which effectors are you studying?
The mechanisms involved in the allergic phenomenon have still not all been deciphered. My previous research focused on mastocytes – immune cells whose activation by the IgEs triggers the release of histamine responsible for allergic symptoms. However, we have also accumulated data demonstrating that the IgEs are not the only immunoglobulins involved in the allergic mechanism. We have shown that the IgGs – another family of immunoglobulins – can also trigger a comparable mechanism. We have obtained these findings through the use of mouse models of anaphylaxis. The question now remains is to find out whether or not the IgGs can also contribute to anaphylactic shock in humans. This is what we are trying to address as part of the project for which I obtained Atip-Avenir funding to form my own team. We are able to study this by combining the use of clinical samples from patients with peanut allergy with a unique humanized mouse model, which was developed in Inserm Unit 1222. In this model, the genes coding for certain mouse receptors to immunoglobulins have been replaced with human receptors, enabling us for the first time to study the mechanisms of shock induced by human antibodies derived from the plasma of allergic patients.
What are the therapeutic horizons for such research?
By understanding the cellular and molecular mechanisms involved, we will be able to identify new therapeutic targets. The underlying idea is to develop novel immunotherapies to treat the allergic diseases. As such, within the framework of the French National Research Agency (ANR) funding – obtained by our Atip-Avenir team in collaboration with Inserm Unit 1222 and the company NEOVACS – we are seeking to develop a therapeutic vaccine to block two cytokines that play a major role in allergy: IL-4 and IL-13. These cytokines are particularly known to promote IgE production. This research could lead to the treatment of some allergic inflammatory diseases, particularly allergic asthma.