The Transcription Factors T-bet and Eomes Control Key Checkpoints of Natural Killer Cell Maturation

By S. Gordon, Julie Chaix, Levi J. Rupp, Junmin Wu, Sharline Madera, Joseph C. Sun, T. Lindsten, S. Reiner. Immunity, 2012

743 citations recorded by the source corpus.

Summary Natural killer (NK) cells play critical roles defending against tumors and pathogens. We show that mice lacking both transcription factors Eomesodermin (Eomes) and T-bet failed to develop NK cells. Developmental stability of immature NK cells constitutively expressing the death ligand TRAIL depended on T-bet. Conversely, maturation characterized by loss of constitutive TRAIL expression and induction of Ly49 receptor diversity and integrin CD49b (DX5+) required Eomes. Mature NK cells from which Eomes was deleted reverted to phenotypic immaturity if T-bet was present or downregulated NK lineage antigens if T-bet was absent, despite retaining expression of Ly49 receptors. Adult, hepatic and fetal hematopoiesis restricted Eomes expression and limited NK development to the T-bet-dependent, immature stage, whereas medullary hematopoiesis permitted Eomes-dependent NK maturation in adult mice. These findings reveal two sequential, genetically separable checkpoints of NK cell maturation, the progression of which is metered largely by the anatomic localization of hematopoiesis.

Subfields: Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/5f40dd80e53299d2bc31522d7ca598fa7ccde48c

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Citations in the corpus

Developmental Relationships of Four Exhausted CD8+ T Cell Subsets Reveals Underlying Transcriptional and Epigenetic Landscape Control Mechanisms (2020, neutral): “(Gordon et al., 2012) Markers typically associated Beltra et al.”
chromVAR: Inferring transcription factor-associated accessibility from single-cell epigenomic data (2017, methodology): “As such, we applied chromVAR to two bulk chromatin accessibility data sets 18,19 down-sampled to 10,000 fragments per sample and data from an alternate scATAC-seq approach and find chromVAR to generalize to these additional data (Supplementary Figs 13–15; Supplementary Note 3).”
Differentiation of type 1 ILCs from a common progenitor to all helper-like innate lymphoid cell lineages. (2014, positive): “Eomes and NFIL3 are transcription factors required for the development of cNK cells (Gascoyne et al., 2009; Gordon et al., 2012; Kamizono et al., 2009).”
Joint probabilistic modeling of single-cell multi-omic data with totalVI (2021, background): “For proteins, totalVI identified CD335 (NKp46) as among the top markers for NK cells, which is a canonical marker used for sorting [42], and CD43, which is associated with the development of NK cells [43].”
Intraepithelial type 1 innate lymphoid cells are a unique subset of cytokine responsive interferon-γ-producing cells (2013, positive): “In contrast, these cells were dramatically reduced in the IEL of mice with knock-out mutations of Nfil3 or Tbx21, which encode two transcription factors previously shown to be master regulators of NK cell development (Gordon et al., 2012; Male et al., 2012) (Figure 6D).”