Interferon-γ constrains cytokine production of group 2 innate lymphoid cells

Fujimi Kudo, Masashi Ikutani, Yoichi Seki, Takeshi Otsubo, Yuki I. Kawamura, Taeko Dohi, Kenshiro Oshima, Masahira Hattori, Susumu Nakae, Kiyoshi Takatsu, Satoshi Takaki*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    26 Citations (Scopus)


    Group 2 innate lymphoid cells (ILC2s) produce a significant amount of interleukin-5 (IL-5), which supports eosinophil responses in various tissues; they also produce IL-13, which induces mucus production and contributes to tissue repair or fibrosis. The ILC2s are activated by alarmins, such as IL-33 released from epithelia, macrophages and natural killer T (NKT) cells in response to infection and allergen exposure, leading to epithelial injury. We examined gene expression in lung ILC2s and found that ILC2s expressed Ifngr1, the receptor for interferon-γ (IFN-γ). Interferon-γ severely inhibited IL-5 and IL-13 production by lung and kidney ILC2s. To evaluate the effects in vivo, we used α-galactosylceramide (α-GalCer) to induce NKT cells to produce IL-33 and IFN-γ. Intraperitoneal injection of α-GalCer in mice induced NKT cell activation resulting in IL-5 and IL-13 production by ILC2s. Administration of anti-IFN-γ together with α-GalCer significantly enhanced the production of IL-5 and IL-13 by ILC2s in lung and kidney. Conversely, cytokine production from ILC2s was markedly suppressed after injection of exogenous IL-33 in Il33-/- mice pre-treated with α-GalCer. Hence, IFN-γ induced or already present in tissues can impact downstream pleiotropic functions mediated by ILC2s, such as inflammation and tissue repair.

    Original languageEnglish
    Pages (from-to)21-29
    Number of pages9
    Issue number1
    Publication statusPublished - 2016 Jan 1


    • Group 2 innate lymphoid cells
    • Interferon-γ
    • Interleukin-13
    • Interleukin-5
    • T helper type 2 cytokines

    ASJC Scopus subject areas

    • Immunology
    • Immunology and Allergy


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