Journal
IMMUNITY
Volume 54, Issue 6, Pages 1320-+Publisher
CELL PRESS
DOI: 10.1016/j.immuni.2021.03.024
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Funding
- NIH [T32 DK077653-27, R01 DE025884, 1R01 AI134236-01, R01 124699, R01 AI134035]
- Merck KGaA (Darmstadt, Germany)
- Chan Zuckerberg Initiative (CZI)
- HHMI International Scholar award
- European Research Council consolidator grant (ERCCOG) [724471]
- ISF Israel Precision Medicine Program (IPMP) [607/20, P128245]
- SCA award of the Wolfson Foundation and Family Charitable Trust
- Thompson Family Foundation, an MRA Established Investigator Award [509044]
- Israel Science Foundation [703/15]
- Ernest and Bonnie Beutler Research Program for Excellence in Genomic Medicine
- Helen and Martin Kimmel award for innovative investigation
- NeuroMac DFG/Transregional Collaborative Research Center Grant
- International Progressive MS Alliance/NMSS [PA-1604 08459]
- Abney Foundation grant
- NWO [019.181EN.038]
- Cancer Research Institute
- European Research Council (ERC) [724471] Funding Source: European Research Council (ERC)
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NK cells and ILC1s are heterogenous innate lymphocytes characterized by specific gene expression programs in different tissues, including blood, spleen, and solid tumors. The programs of circulating NK cells were found to be reshaped in tumor-bearing mice, with conserved signatures similar to human NK cells. This study advances the understanding of the NK-ILC1 spectrum in both murine and human systems.
Natural killer (NK) cells and type 1 innate lymphoid cells (ILC1s) are heterogenous innate lymphocytes broadly defined in mice as Lin(-) NK1.1(+)NKp46(+) cells that express the transcription factor T-BET and produce interferon-gamma. The ILC1 definition primarily stems from studies on liver and small intestinal populations. However, NK1.1(+)NKp46(+) cells in the salivary glands, uterus, adipose, and other tissues exhibit nonuniform programs that differ from those of liver or intestinal ILC1s or NK cells. Here, we performed single-cell RNA sequencing on murine NK1.1(+)NKp46(+) cells from blood, spleen, various tissues, and solid tumors. We identified gene expression programs of tissue-specific ILC1s, tissue-specific NK cells, and non-tissue-specific populations in blood, spleen, and other tissues largely corresponding to circulating cells. Moreover, we found that circulating NK cell programs were reshaped in tumor-bearing mice. Core programs of circulating and tumor NK cells paralleled conserved human NK cells signatures, advancing our understanding of the human NK-ILC1 spectrum.
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