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

Marina Cella, Ramya Gamini, Cristiane Sécca, Patrick L. Collins, Shanrong Zhao, Vincent Peng, Michelle L. Robinette, Jorge Schettini, Konstantin Zaitsev, William Gordon, Jennifer K. Bando, Kentaro Yomogida, Victor Cortez, Catrina Fronick, Robert Fulton, Lih Ling Lin, Susan Gilfillan, Richard A. Flavell, Liang Shan, Maxim N. ArtyomovMichael Bowman, Eugene M. Oltz, Scott A. Jelinsky, Marco Colonna

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

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.

Original languageEnglish
Pages (from-to)980-991
Number of pages12
JournalNature immunology
Volume20
Issue number8
DOIs
StatePublished - Aug 1 2019

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