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Learn MoreRegulatory T (Treg) cells maintain self-tolerance in lymphoid tissues, and specialized Treg cells accumulate and perform homeostasis and regenerative functions in non-lymphoid tissues. A common differentiation pathway of homeostasis-promoting Treg cells in non-lymphoid tissues from a putative precursor remains elusive. By using novel reporter mice and single-cell RNA-sequencing, we identified precursor stages of the IL-33 receptor ST2-expressing non-lymphoid tissue Treg population in spleen and lymph nodes. Molecular profiling of these precursors versus mature tissue Treg cells revealed their sequence of differentiation on a single-cell level. Global chromatin profiling of non-lymphoid tissue Treg cells and progenitor populations revealed a stepwise acquirement of open chromatin accessibility at tissue Treg genes. Mechanistically, we identified and validated the basic leucine zipper transcription factor, ATF-like (Batf) as a driver of the molecular tissue Treg program. Understanding this tissue program will help to harness regenerative properties of tissue Treg cells for therapy. SOURCE: Markus Feuerer (markus.feuerer@ukr.de) - Immunology Regensburg Center for Interventional Immunology
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