TABANK · Targeting B cell Activation driven by Natural Killer cells

Targeting B cell Activation driven by Natural Killer cells

Autoimmune diseases affect nearly 4% of the world’s population and can be life-threatening. Among them, Sjögren’s Disease (SjD) 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 SjD and promising drugs targeting B cell activation are currently under phase 3 clinical trials. Restraining B cell hyperactivity is central to treat SjD permanently. Hence, instead of targeting B cell activation, SjD treatments would also benefit from targeting signals or interactions leading to B cell activation. Targeting interaction leading to B cell hyperactivity will enable the first-ever study investigating B cell hyperactivity in relation to other immune cells in SjD. Our main hypothesis is that treatment should focus on Targeting B cell Activation driven by Natural Killer (NK) cells (TABANK), a cell type (i) located within the inflamed tissues; (ii) involved in the first line of defense against pathogen; (iii) that produce cytokines and chemokines known to act on B cells (BAFF, FLT3, IFN) and (iv) which could directly interact with B cells. TABANK proposes to investigate this unique “marriage” of immune cells using cutting-edge technologies (high-parameter flow cytometry, single-cell sequencing technologies and unsupervised analysis) to interrogate the immune network in the circulation of SjD 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 profile in SjD using cutting both-single cell sequencing on high-parameter mass and flow cytometry; ii) Determining potential interaction of immune cells leading to B cell-activation using a novel computational approach; and iii) Defining and validating these interactions using ex vivo culture. This new approach will provide a critical, and as yet still-missing, link needed to refine uncertainties on the cellular and molecular interactions that lead to an exacerbated immune response. TABANK results could then be used to find potential new treatments to cure SjD.

Data: CORDIS, © European Union