Autoimmunity can cause severe tissue damage since regulation of immune cells that target healthy cells is failing. Lymph nodes are one of the organs regulating autoreactive immune cells. Here, stromal cells present self-antigens to control autoreactive immune cells. However, regulators of self-antigen expression in lymph node stromal cells are still unknown. By using a whole-genome CRISPR activation screen and validation in vitro, ex vivo and in vivo, we aim to identify these regulatory factors. Discovering these regulators will give more insights in fundamental mechanisms of autoimmunity and might be used to design new therapeutic strategies.