BACH2 drives quiescence and maintenance of resting Treg cells to promote homeostasis and cancer immunosuppression

Francis M. Grant, Jie Yang, Rabab Nasrallah, James Clarke, Firas Sadiyah, Sarah K. Whiteside, Charlotte J. Imianowski, Paula Kuo, Panagiota Vardaka, Tihomir Todorov, Nordin Zandhuis, Ilinca Patrascan, David F. Tough, Kohei Kometani, Robert Eil, Tomohiro Kurosaki, Klaus Okkenhaug, Rahul Roychoudhuri

    Research output: Contribution to journalArticlepeer-review

    8 Scopus citations

    Abstract

    Regulatory T (Treg) cell populations are composed of functionally quiescent resting Treg (rTreg) cells which differentiate into activated Treg (aTreg) cells upon antigen stimulation. How rTreg cells remain quiescent despite chronic exposure to cognate self- and foreign antigens is unclear. The transcription factor BACH2 is critical for early Treg lineage specification, but its function following lineage commitment is unresolved. Here, we show that BACH2 is repurposed following Treg lineage commitment and promotes the quiescence and long-term maintenance of rTreg cells. Bach2 is highly expressed in rTreg cells but is down-regulated in aTreg cells and during inflammation. In rTreg cells, BACH2 binds to enhancers of genes involved in aTreg differentiation and represses their TCR-driven induction by competing with AP-1 factors for DNA binding. This function promotes rTreg cell quiescence and long-term maintenance and is required for immune homeostasis and durable immunosuppression in cancer. Thus, BACH2 supports a division of labor between quiescent rTreg cells and their activated progeny in Treg maintenance and function, respectively.

    Original languageEnglish (US)
    Article numberjem.20190711
    JournalJournal of Experimental Medicine
    Volume217
    Issue number9
    DOIs
    StatePublished - Sep 7 2020

    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology

    Fingerprint Dive into the research topics of 'BACH2 drives quiescence and maintenance of resting Treg cells to promote homeostasis and cancer immunosuppression'. Together they form a unique fingerprint.

    Cite this