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

Michael Delacher1, Charles D Imbusch2, Agnes Hotz-Wagenblatt3

  • 1Regensburg Center for Interventional Immunology (RCI), Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany; Chair for Immunology, Regensburg University, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany; Immune Tolerance Group, Tumor Immunology Program, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.

Immunity
|January 12, 2020
PubMed

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.

Keywords:
ATAC-seqAregBatfFoxp3Gata3Nfil3precursorscRNA-seqscTCR-seqtissue Treg

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