Autoimmune diseases can affect the lungs, and the mechanisms used to prevent autoimmune lung disease are incompletely understood. Recent studies in the thymus have identified unique populations of medullary thymic epithelial cells (mTECs) called mimetic cells that transcriptionally mimic peripheral epithelial populations. These mimetic cells have important functions in the thymus in immune tolerance. Here, we used a mouse line with thymic-specific deletion of Runt-related transcription factor 1 (Runx1) to identify a new mimetic cell akin to alveolar type 2 (AT2) lung epithelial cells. AT2 mTECs express surfactant genes, and with Runx1 deletion AT2 mTECs expand, resulting in a loss of AIRE+mTECs and defects in T cell selection. RUNX1 suppresses AT2 mTECs by inhibiting epidermal growth factor receptor signaling. Together, our results identify a thymic mimetic cell type that mimics lung AT2 epithelial cells, further uncovering unrealized epithelial diversity in the thymus.
https://doi.org/10.1038/s41590-026-02536-0
