immgenT Treg: A Reference Landscape of Regulatory T Cell States in Mice

CD4+Foxp3+ regulatory T cells (Tregs) are central to immunity, tolerance, and tissue homeostasis, yet their extensive heterogeneity lacks a unifying framework. immgenT-Treg is a comprehensive molecular atlas of mouse Treg cells spanning organs and disease states, integrating more than 44,000 single cells from over 700 samples with gene expression, 128-plex surface protein profiling, and paired TCR sequencing. Using a joint RNA-protein deep generative model, we define a finite Treg landscape organized around eight conserved clusters shared across tissues and conditions, with immune context reshaping their relative abundance rather than generating new Treg states, including a prominent circulating effector Treg population enriched in select non-lymphoid tissues. We validate this framework by integrating external datasets from conditions not represented in immgenT and by defining an eight-marker flow cytometry panel spanning the Treg landscape. Together, immgenT provides a scalable, reusable reference that unifies Treg heterogeneity across tissues and immune challenges.