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

Erin C. Zook, Zhong Yin Li, Yiying Xu, Renée F. de Pooter, Mihalis Verykokakis, Aimee Beaulieu, Anna Lasorella, Mark Maienschein-Cline, Joseph C. Sun, Mikael Sigvardsson, Barbara L. Kee

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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+CD11b cells that failed to differentiate into CD27CD11b+ cytotoxic effectors. We show that ID2 limited chromatin accessibility at E protein binding sites near naïve 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 naïve T cells, and they transitioned from a CD8 memory precursor–like to a naïve-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 naïve 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.

Original languageEnglish (US)
Article numbereaao2139
JournalScience Immunology
Volume3
Issue number22
DOIs
StatePublished - Jan 1 2018
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

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. (2018). Transcription factor ID2 prevents E proteins from enforcing a naïve T lymphocyte gene program during NK cell development. Science Immunology, 3(22), [eaao2139]. https://doi.org/10.1126/sciimmunol.aao2139