Emily Stuchfield-Denby, lauréate du prix Alternatives Research & Development Foundation

Félicitation à Emily Stuchfield-Denby et Xavier Moisset pour l’obtention de la bourse de la Alternatives Research & Development Foundation (USA) , d’un montant de 29 691$

Le projet déposé était le suivant :

Migraine is a frequent and disabling disorder with significant social and economic impact worldwide. It occurs more frequently in women and patients with autoimmune or inflammatory diseases. Cytokine and immune cell dysregulations have been evidenced in the disease and inflammation seems to play an important role in migraine chronification, but the role of inflammation in migraine pathophysiology remains unclear. Regulatory T (Treg) lymphocytes are important in maintaining immune homeostasis. They regulate pro-inflammatory effector T (Teff) cells and cytokine release through different suppressive mechanisms such as the hydrolysis of adenosine triphosphate (ATP) into adenosine (ADO), by Treg surface enzymes CD39 and CD73. ATP is involved in the transduction of pain signals in migraine, and its insufficient hydrolysis can lead to pain chronification. Recent studies suggest altered Treg proportions in migraine, with decreased CD39-positive Treg cells. This further suggests altered Treg suppressive functions, but no functional assays have been led to confirm that. We aim to show that Treg suppressive functions are altered in migraine and that the ADO pathway is deficient. Through Treg/Teff coculture we will measure the ability of Tregs to inhibit Teff proliferation and cytokine secretion and assess the CD39-related hydrolytic activity of Tregs. It is important to us to reduce laboratory animal use in our experiments and in reagent production. Therefore, our study completely relies on human tissue for analysis and the reagents we intend to use are made using animal-free methods. This study, following the ‘3Rs’ principle, should lead to a better understanding of migraine pathophysiology and the development of personalized treatments according to the immune pain profile of migraine patients. This work will demonstrate the power of animal-free and human-based experimentation for immune-cell testing.