Precursors for Nonlymphoid-Tissue Treg Cells Reside in Secondary Lymphoid Organs and Are Programmed by the Transcription Factor BATF

作者：Michael Delacher, Charles David Imbusch, Agnes Hotz‐Wagenblatt, Jan‐Philipp Mallm, Katharina Bauer, Malte Simon, Dania Riegel, André F. Rendeiro, Sebastian Bittner, Lieke Sanderink, Asmita Pant, Lisa M. Schmidleithner, Kathrin Luise Braband, Bernd Echtenachter, Alexander H. Fischer, Valentina Giunchiglia, Petra Hoffmann, Matthias Edinger, Christoph Bock, Michael Rehli, Benedikt Brors, Christian Schmidl, Markus Feuerer · 发表于：Immunity · 年份：2020 · DOI：10.1016/j.immuni.2019.12.002 · 被引用次数：284 · 研究领域：IL-33, ST2, and ILC Pathways、Immune Cell Function and Interaction、T-cell and B-cell Immunology

Specialized regulatory T (Treg) cells accumulate and perform homeostatic and regenerative functions in nonlymphoid tissues. Whether common precursors for nonlymphoid-tissue Treg cells exist and how they differentiate remain elusive. Using transcription factor nuclear factor, interleukin 3 regulated (Nfil3) reporter mice and single-cell RNA-sequencing (scRNA-seq), we identified two precursor stages of interleukin 33 (IL-33) receptor ST2-expressing nonlymphoid tissue Treg cells, which resided in the spleen and lymph nodes. Global chromatin profiling of nonlymphoid tissue Treg cells and the two precursor stages revealed a stepwise acquisition of chromatin accessibility and reprogramming toward the nonlymphoid-tissue Treg cell phenotype. Mechanistically, we identified and validated the transcription factor Batf as the driver of the molecular tissue program in the precursors. Understanding this tissue development program will help to harness regenerative properties of tissue Treg cells for therapy.