Dendritic cells (DCs) are key regulators of self-tolerance, yet the molecular mechanisms governing self-tolerance and their loss in autoimmunity remain elusive. Leveraging single-cell genomics, we propose a systematic framework to identify and prioritize regulators of DC function across autoimmunity.

We will first generate a unified atlas of DC states across human and mouse autoimmunity, capturing inflammatory and tolerogenic programs. Building on this, in vivo DC-CRISPR-seq will enable pooled CRISPR screening of candidate regulators directly within autoimmunity.

This approach offers a scalable strategy to identify actionable control points in DC biology and guide the development of tolerogenic therapies for autoimmune diseases.