2. Academic Validation
  3. Differentiation of c-Kit+ CD24+ natural killer cells into myeloid cells in a GATA-2-dependent manner

Differentiation of c-Kit+ CD24+ natural killer cells into myeloid cells in a GATA-2-dependent manner

  • FASEB J. 2020 Mar;34(3):4462-4481. doi: 10.1096/fj.201902662R.
Boyeong Song 1,  Jeong-Mi Lee 2,  Young-Jun Park 3,  Il-Kyu Kim 4,  Byung-Seok Kim 3,  Kwang-Soo Shin 2,  Insu Jeon 1,  Choong-Hyun Koh 2,  Eun-Ah Bae 1,  Hyungseok Seo 1 4,  Youngro Byun 5,  Chang-Yuil Kang 1 2
Affiliations

Affiliations

  • 1 Laboratory of Immunology, Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Republic of Korea.
  • 2 Laboratory of Immunology, College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
  • 3 Laboratory of Immune Regulation, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
  • 4 Laboratory of Immunology, Research Institute of Pharmaceutical Science, College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
  • 5 Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Republic of Korea.
PMID: 31989715 DOI: 10.1096/fj.201902662R
Abstract

Myeloid progenitor cells have generally been considered the predominant source of myeloid cells under steady-state conditions. Here we show that NK cells contributed to a myeloid cell lineage pool in naïve and tumor-bearing mice. Using fate tracing of NKp46+ cells, we found that myeloid cells could be derived from NK cells. Notably, among mature CD11b+ CD27+ NK cells, c-Kit+ CD24+ NK cells were capable of differentiating into a range of myeloid lineages in vitro and produced neutrophils and monocytes in vivo. The differentiation was completely inhibited by NK-stimulating cytokines. In addition to the potential for differentiation into myeloid cells, c-Kit+ CD24+ NK cells retained NK cell phenotypes and effector functions. Mechanistically, GATA-2 was necessary for the differentiation of c-Kit+ CD24+ NK cells. Therefore, we discovered that GATA-2-dependent differentiation of c-Kit+ CD24+ NK cells contributes to myeloid cell development and identified a novel pathway for myeloid lineage commitment under physiological conditions.

Keywords

CD24; GATA-2; c-Kit; myeloid cell development; natural killer cell.

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