Targeting B cell Activation driven by Natural Killer cells

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Autoimmune diseases affect nearly 4% of the world’s population and can be life-threatening. Among them, primary Sjögren Syndrome (pSS) is the most common systemic autoimmune disease. Unfortunately, to date, treatments are focusing on relieving symptoms. It is of public relevance to find potential new biomarkers for treatments. B cells are one key player in pSS and promising drugs targeting B cell activation are currently under phase 3 clinical trials. Restraining B cell hyperactivity is central to treating pSS permanently. Hence, instead of targeting B cell activation, pSS treatments would also benefit from targeting signals or interactions leading to B cell activation. The TABANK project aims to address this hypothesis by using cutting-edge technologies (high-parameter flow cytometry, single-cell sequencing technologies and unsupervised analysis) to interrogate the immune network in the circulation of pSS donors as well as in the inflamed environment of impaired salivary glands. This overarching goal will be achieved by (i) Compiling a comprehensive database of immune cell profiles in pSS using both single-cell sequencing and high-parameter mass and flow cytometry; (ii) Determining potential interactions of immune cells leading to B cell activation using a novel computational approach; and (iii) Validating these interactions using ex vivo culture. TABANK will be conducted at the Lymphocytes B, Autoimmunity and Immunotherapies center, Université of Brest Occidentale a leading research institution in the study of immunotherapies for B cell diseases. This project will be supervised by two leading experts in autoimmune diseases and B cell biology. This unique synergy, in addition the researcher’s own expertise in examining immune responses in human tissues, particularly oral mucosal tissues, will precondition the project for success while facilitating a mutually beneficial, two-way transfer of knowledge.