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Nat Immunol. 2019 Jun 17. doi: 10.1038/s41590-019-0425-y. [Epub ahead of print]

Subsets of ILC3-ILC1-like cells generate a diversity spectrum of innate lymphoid cells in human mucosal tissues.

Author information

1
Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, USA.
2
Pfizer Worldwide Research and Development, Cambridge, MA, USA.
3
Department of Microbial Infection and Immunity, Ohio State University, Wexner School of Medicine, Columbus, OH, USA.
4
Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
5
Computer Technologies Department, ITMO University, St Petersburg, Russia.
6
Cogen Therapeutics, Cambridge, MA, USA.
7
Department of Microbiology and Immunology, University of California, San Francisco, CA, USA.
8
The McDonnell Genome Institute, Washington University School of Medicine, St Louis, MO, USA.
9
Immunology and Inflammation, Sanofi, Cambridge, MA, USA.
10
Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.
11
Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT, USA.
12
Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St Louis, MO, USA.
13
Pfizer Worldwide Research and Development, Cambridge, MA, USA. Scott.Jelinsky@pfizer.com.
14
Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, USA. mcolonna@wustl.edu.

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.

PMID:
31209406
DOI:
10.1038/s41590-019-0425-y

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