@article{f43f9f48841b4eda9c2b8fef9994cb8e,
title = "Subsets of ILC3−ILC1-like cells generate a diversity spectrum of innate lymphoid cells in human mucosal tissues",
abstract = "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-γ 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.",
author = "Marina Cella and Ramya Gamini and Cristiane S{\'e}cca and Collins, {Patrick L.} and Shanrong Zhao and Vincent Peng and Robinette, {Michelle L.} and Jorge Schettini and Konstantin Zaitsev and William Gordon and Bando, {Jennifer K.} and Kentaro Yomogida and Victor Cortez and Catrina Fronick and Robert Fulton and Lin, {Lih Ling} and Susan Gilfillan and Flavell, {Richard A.} and Liang Shan and Artyomov, {Maxim N.} and Michael Bowman and Oltz, {Eugene M.} and Jelinsky, {Scott A.} and Marco Colonna",
note = "Funding Information: We thank the Genome Technology Access Center in the Department of Genetics at Washington University School of Medicine for help with genomic analysis. The Center is partially supported by NCI Cancer Center Support grant no. P30 CA91842 to the Siteman Cancer Center and by ICTS/CTSA grant no. UL1 TR000448 from the National Center for Research Resources. We thank E. Lantelme and D. Brinja, and the Pathology and Immunology Flow Cytometry Core for cell sorting. We thank O. Malkova, R. Lin and S. Oh, and the Center for Human Immunology at Washington University for help in processing the samples for mass spectrometry and for advice on analysis. We thank the Washington University Digestive Disease Research Core (NIDDK P30 DK052574) for support. We thank Regeneron for providing MISTRG-6 and IL-15 humanized mice. We thank S. Henikoff (Fred Hutchison Cancer Research Center, Seattle, USA) for providing protein-A-Mnase. This work was in part supported by grant nos UO1 AI095542 and RO1 DE025884 (to M. Colonna) and RO1 AI134035 (to M. Colonna and E.M.O.). R.A.F. is supported by the Howard Hughes Institute. Publisher Copyright: {\textcopyright} 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.",
year = "2019",
month = aug,
day = "1",
doi = "10.1038/s41590-019-0425-y",
language = "English",
volume = "20",
pages = "980--991",
journal = "Nature Immunology",
issn = "1529-2908",
number = "8",
}