Project name: BACH2 restricts NK cell maturation and function limiting immunity to cancer metastasis

Description: Natural killer (NK) cells are critical to immune surveillance against infections and cancer. Their role in immune surveillance requires that NK cells are present within tissues in a quiescent state. Mechanisms by which NK cells remain quiescent in tissues are incompletely elucidated. The transcriptional repressor BACH2 plays a critical role within the adaptive immune system, but its function within innate lymphocytes has been unclear. Here, we show that BACH2 acts as an intrinsic negative regulator of NK cell maturation and function. BACH2 is expressed within developing and mature NK cells and promotes the maintenance of immature NK cells by restricting their maturation in the presence of weak stimulatory signals. Loss of BACH2 within NK cells results in accumulation of activated NK cells with unrestrained cytotoxic function within tissues, which mediate augmented immune surveillance to pulmonary cancer metastasis. These findings establish a critical function of BACH2 as a global negative regulator of innate cytotoxic function and tumor immune surveillance by NK cells.Overall design: WT or Bach2-deficient NK cells fractionated into subsets were sorted from spleens of cWT (Ncr1Cre) or cKO (Bach2flox/flox Ncr1Cre) animals and subjected to RNA-Seq (experiment CI0146). Bulk WT and Bach2-KO cells were sorted from spleens of mixed bone marrow chimeric animals reconstituted with ~1:1 mixtures of WT and Bach2-KO bone marrow cells (CI056). WT NK cell subsets were also sorted from spleens of WT animals (CI056). Total RNA extracted and sequenced. Experiments described in Imianowski et al, J Exp Med, 2022

Data type: Transcriptome or Gene expression

Sample scope: Multiisolate

Relevance: ModelOrganism

Last updated: 2022-09-24