Atopic dermatitis is an inflammatory skin disease affecting up to 20% of children and 5% of adults in the western world. Their quality of life is impaired by pain and intense itching. Nicolas Gaudenzio* wishes to create a synergy among multiple disciplines in order to better understand their disease and to evaluate how their immune cells interact with other components, particularly the nerve fibers. The researcher has recently obtained a European Research Council (ERC) Starting Grant to help him do just that.
Is there anything we still do not know about such a common disease as atopic dermatitis?
Atopic dermatitis is a disease with an allergic component whose origin remains poorly understood. I have had a passionate interest in immune response since my Masters, and have spent a lot of time studying the mechanisms that regulate these allergic responses. In atopic dermatitis, in parallel to the exacerbation of the immune response by the type 2 lymphocytes (specific to allergic phenomena), we also observe neuron damage associated with intense itching. It is important to understand whether there is an interaction between the immune and neuronal mechanisms and, if so, what it is.
It could be thought that the immune dysfunction leads to the development of itching. But we do not know which event occurs first during the development of the pathology. Recent data suggest that outside of their primary function in the transmission of sensations, the sensory neurons have an unknown role in regulating the immune players: this is referred to as "neuronal control of immune response", a mechanism which is starting to be described in other experimental models, such as asthma. We would like to know whether this same mechanism also exists in inflammatory skin diseases, such as atopic dermatitis.
What approaches will you use to study this question?
Many human diseases, despite being multifactorial, are studied discipline by discipline. I obtained ERC funding in order to develop a multidisciplinary approach to the study of atopic dermatitis. My project is called IMMCEPTION, a contraction of the words "immunity" and "nociception". It is devoted to neuroimmunology and will incorporate expertise in immunology, neurobiology, clinical dermatology and information technology. We will study the interactions between the peripheral nervous system, particularly sensory, and the development of the allergic immune response at skin level. The genetic aspect will also be incorporated given that some genes appear to be involved in the pathophysiology of this disease.
While atopic dermatitis is our focus at present, we are not ruling out the subsequent study of other diseases, in order to find out whether the mechanisms that we identify are maintained in other diseases and organs. There is the potential for new therapeutic targets to be identified based on our discoveries.
To what extent will the ERC Starting Grant enable you to explore this question?
We are working in parallel on mouse models of the disease and on skin samples taken directly from atopic dermatitis patients. Our research blends biological analysis, genetic analysis and imaging, with my specialism being fluorescence imaging. We have data obtained in vivo by intravital two-photon microscopy. It is an innovative approach which offers spatial and temporal resolution essential for understanding the biological mechanisms that regulate the development of the disease.
This 1.5-million-euro funding over five years offers me the possibility to form a team of five or six people from the outset and to remain in competition with the international laboratories who are also working on this subject. With the ATIP-Avenir label which I obtained in parallel, our laboratory will have internationally-renowned markers of excellence, important not just for recruitment but also for the international visibility of our projects.
*Unit 1056 Inserm/Université Paul Sabatier Toulouse 3, Epidermal differentiation and rheumatoid autoimmunity, Toulouse