Narrowing Down Key Players in Autoimmunity via Single-Cell Multiomics

Autoimmune diseases encompass a range of conditions in which our own immune system reacts against molecules encoded by our own genome. This phenomenon is mediated by the action of antigen receptors expressed by T and B cells. Identifying the molecular events that trigger these responses as well as the effector cells that underlie them is at the heart of autoimmunity research. In this review, we discuss how single-cell multiomics techniques applied to healthy and patient tissues are shedding light on the mechanisms underpinning autoimmune conditions, specifically by identifying disease-associated cell states and cellular communication networks, including those linked to specific autoimmunity susceptibility genetic loci. Furthermore, we dive into the unprecedented resolution achieved in mapping autoreactive lymphocytes, a key component of autoimmune responses. We conclude with a perspective on key bottlenecks and promising future directions leveraging the latest advances in single-cell sequencing with orthogonal methods.