期刊
CELL RESEARCH
卷 31, 期 5, 页码 554-568出版社
SPRINGERNATURE
DOI: 10.1038/s41422-020-00445-x
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资金
- Swedish National Infrastructure for Computing (SNIC) [SNIC 2017/7-123]
- Knut and Alice Wallenberg Foundation as part of the National Bioinformatics Infrastructure Sweden at SciLifeLab
- Swedish Cancer Society
- Swedish Foundation for Strategic Research
- Swedish Foundation for Medical Research
- Swedish Research Council
- Knut and Alice Wallenberg foundation
- Karolinska Institutet
This study utilized single-cell RNA sequencing to uncover tissue-specific transcriptional profiles and heterogeneity of CD127(+) ILCs in four human tissues. It identified migratory properties, tissue-residency, activation, and modified metabolism characteristics of ILCs in different tissues. The study also revealed potential differentiation pathways from naive to mature ILC subsets, and unique TCR-V(D)J-rearrangement patterns of blood ILC1-like cells.
The impact of the microenvironment on innate lymphoid cell (ILC)-mediated immunity in humans remains largely unknown. Here we used full-length Smart-seq2 single-cell RNA-sequencing to unravel tissue-specific transcriptional profiles and heterogeneity of CD127(+) ILCs across four human tissues. Correlation analysis identified gene modules characterizing the migratory properties of tonsil and blood ILCs, and signatures of tissue-residency, activation and modified metabolism in colon and lung ILCs. Trajectory analysis revealed potential differentiation pathways from circulating and tissue-resident naive ILCs to a spectrum of mature ILC subsets. In the lung we identified both CRTH2(+) and CRTH2(-) ILC2 with lung-specific signatures, which could be recapitulated by alarmin-exposure of circulating ILC2. Finally, we describe unique TCR-V(D)J-rearrangement patterns of blood ILC1-like cells, revealing a subset of potentially immature ILCs with TCR-delta rearrangement. Our study provides a useful resource for in-depth understanding of ILC-mediated immunity in humans, with implications for disease.
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