Year: 2022
Type: article
Abstract: Natural killer (NK) cells are the predominant innate lymphoid cells that mediate anti-viral and anti-tumor immunity. NK cells arise from hematopoietic stem cells in the bone marrow (BM) and undergo lineage specification and maturation. Despite the importance of NK cells for innate immunity and the development of innovative cancer therapy, the detailed steps linking NK progenitor (NKP) cell development through immature NK (iNK) cells to mature NK (mNK) cells are poorly defined. In this study, we found that CD49b, NK1.1, and NKp46 are sequentially acquired during the development of murine Lin−CD122+ NKP cells. Introducing NKp46 allows us to propose a four-stage developmental model, wherein CD122+NK1.1−CD49b−NKp46− defines an NKP population, CD122+NK1.1−CD49b+NKp46− and CD122+NK1.1+CD49b−/+ NKp46− define iNK-a and iNK-b populations, respectively, and CD122+NK1.1+CD49b+NKp46+ defines an mNK population. These four NK cell populations are phenotypically distinct based on their expression of cell surface markers, transcription factors, and effector molecules. Using a differentiation assay ex vivo and adoptive transfer model in vivo, we confirmed that NK cell development follows our predicted four-stage model. Taken together, our findings establish two distinct populations of immature NK cells and define a model for mouse NK cell development.
Source: Journal of Hematology & Oncology
Authors: Shoubao Ma, Michael A. Caligiuri, Jianhua Yu
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,190
Awards: Overcoming Barriers of Virotherapy by Next-Generation oHSV Expressing E-Cadherin, Enhancing NK Cell Activity by Dietary Diphyllin Lignans for Cancer Prevention, G2397580644, Elucidate and Modulate Cell Signaling in NK Cells for Glioma Treatment, scFvPD1-FLT3 CAR T Cells for the Treatment of Relapsed Acute Myeloid Leukemia, Characterizing and Targeting the Novel IL-15- AKT-XBP1s Pathway in NK Cells, G9000145997, G9000226092, Human natural killer cells: Advancing biology and clinical applications, Targeting FLT3 for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia, Development of Small Molecule Inhibitors and Biologic Agents for Treatment of Glioblastoma Using Intracerebral Microdialysis and Signatures of Vulnerability, Phase 1 Evaluation of Enhanced Natural Killer Cells as a Treatment Strategy in Non-Small cell Lung Cancer Patients Refractory to PD-1/PD-L1 Immune Checkpoint Inhibitors, Circumventing Barriers to Effective Oncolytic Virotherapy of Malignant Gliomas
OpenAlex ID: W4220661649