Transcription factor ID2 prevents E proteins from enforcing a naive T lymphocyte gene program during NK cell development Journal Article


Authors: Zook, E. C.; Li, Z. Y.; Xu, Y.; de Pooter, R. F.; Verykokakis, M.; Beaulieu, A.; Lasorella, A.; Maienschein-Cline, M.; Sun, J. C.; Sigvardsson, M.; Kee, B. L.
Article Title: Transcription factor ID2 prevents E proteins from enforcing a naive T lymphocyte gene program during NK cell development
Abstract: All innate lymphoid cells (ILCs) require the small helix-loop-helix transcription factor ID2, but the functions of ID2 are not well understood in these cells. We show that mature natural killer (NK) cells, the prototypic ILCs, developed in mice lacking ID2 but remained as precursor CD27(+)CD11b3(-) cells that failed to differentiate into CD27(-)CD11b(+) cytotoxic effectors. We show that ID2 limited chromatin accessibility at E protein binding sites near naive T lymphocyte-associated genes including multiple chemokine receptors, cytokine receptors, and signaling molecules and altered the NK cell response to inflammatory cytokines. In the absence of ID2, CD27(+)CD11b(-) NK cells expressed ID3, a helix-loop-helix protein associated with naive T cells, and they transitioned from a CD8 memory precursor-like to a naive-like chromatin accessibility state. We demonstrate that ID3 was required for the development of ID2-deficient NK cells, indicating that completely unfettered E protein function is incompatible with NK cell development. These data solidify the roles of ID2 and ID3 as mediators of effector and naive gene programs, respectively, and revealed a critical role for ID2 in promoting a chromatin state and transcriptional program in CD27(+)CD11b(-) NK cells that supports cytotoxic effector differentiation and cytokine responses.
Keywords: memory; differentiation; expression; generation; cutting edge; progenitors; natural-killer-cells; distinct; innate; e2a
Journal Title: Science Immunology
Volume: 3
Issue: 22
ISSN: 2470-9468
Publisher: Amer Assoc Advancement Science  
Date Published: 2018-04-27
Start Page: eaao2139
Language: English
ACCESSION: WOS:000434333600004
DOI: 10.1126/sciimmunol.aao2139
PROVIDER: wos
PUBMED: 29703840
PMCID: PMC6750718
Notes: Article -- UNSP eaao2139 -- Source: Wos
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  1. Joseph C Sun
    94 Sun