Atopic diseases cause major morbidity and economic loss. Although rare immune cells, basophils are implicated in the pathogenesis of allergic diseases of respiratory system and skin (including rhinitis, asthma and atopic dermatitis), and also autoimmune and other inflammatory diseases like bullous pemphigoid, chronic urticaria and eosinophilic oesophagitis. Considering the impact of dysregulated basophil functions on the pathogenesis of various diseases, it is conceivable that basophils are the potential therapeutic targets. However, currently, there are no specific approaches to target them. In this fundamental-translational project (“BASIN”), we design and investigate an innovative immunotherapeutic approach to inhibit basophil activation in pathological conditions. As IL-3 cytokine, secreted mainly by T cells is the most potent activator of basophils and also a pre-requisite for IgE-mediated degranulation, we hypothesize that interfering with basophil-IL-3 axis will suppress basophil activation and hence benefit allergic and inflammatory diseases. To address this hypothesis, three objectives are planned in BASIN project by combining the complementary expertise of 4 partners in human immunology (Dr. J Bayry), patient tissues (Dr. K Boniface and Pr. J Seneschal), in vivo experimental models (Dr. M Li ), and bioinformatics (Dr. A G De Brevern). Objective 1 is aimed at cross-talk between human basophils and T cells, with a particular focus on regulatory T cells (Tregs), based on our newly published report showing that Tregs induce activation of basophils by IL-3 and STAT5-dependent mechanisms. This task involves both in vitro studies and in situ using allergic patients’ biopsies. Objective 2 is aimed at exploring the IL-3 signal axis in the recruitment and activation of basophils in the inflamed skin tissue, and the mechanisms underlying the loop regulation between basophils and T cells, by using novel genetically modified mouse tools (Il3-reporter mouse line, and Il3-conditional knockout), and atopic dermatitis models. Objective 3 aims at using bioinformatics approach for identification and validation of inhibitors to interfere IL-3 axis, thus to inhibit inflammatory basophil responses in atopic diseases. BASIN project is at the boundary of fundamental and clinical research and aims at translating fundamental findings for the benefit of the individuals and the society. We expect to achieve a better understanding of the expression and function of IL-3 in basophil-mediated inflammation, from cellular cross-talk to molecular signaling both in human and mice. If successful, this translational research brings promising new biotechnological innovations for the therapy of allergy and other inflammatory diseases where basophils and IL-3 are pathogenic. Hence our project has dramatic repercussions for the quality of life of the patients and in the long term reduces societal costs.