期刊
NATURE IMMUNOLOGY
卷 20, 期 8, 页码 980-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41590-019-0425-y
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资金
- NCI Cancer Center Support grant [P30 CA91842]
- ICTS/CTSA from the National Center for Research Resources [UL1 TR000448]
- Washington University Digestive Disease Research Core (NIDDK) [P30 DK052574]
- Howard Hughes Institute
- [UO1 AI095542]
- [RO1 DE025884]
- [RO1 AI134035]
Innate lymphoid cells (ILCs) are tissue-resident lymphocytes categorized on the basis of their core regulatory programs and the expression of signature cytokines. Human ILC3s that produce the cytokine interleukin-22 convert into ILC1-like cells that produce interferon-gamma in vitro, but whether this conversion occurs in vivo remains unclear. In the present study we found that ILC3s and ILC1s in human tonsils represented the ends of a spectrum that included additional discrete subsets. RNA velocity analysis identified an intermediate ILC3-ILC1 cluster, which had strong directionality toward ILC1s. In humanized mice, the acquisition of ILC1 features by ILC3s showed tissue dependency. Chromatin studies indicated that the transcription factors Aiolos and T-bet cooperated to repress regulatory elements active in ILC3s. A transitional ILC3-ILC1 population was also detected in the human intestine. We conclude that ILC3s undergo conversion into ILC1-like cells in human tissues in vivo, and that tissue factors and Aiolos were required for this process.
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