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

    Research output: Contribution to journalArticle

    17 Citations (Scopus)

    Abstract

    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
    JournalImmunology
    Volume147
    Issue number1
    DOIs
    Publication statusPublished - 2016 Jan 1

    Fingerprint

    Interleukin-13
    Interleukin-5
    Interferons
    Natural Killer T-Cells
    Lymphocytes
    Cytokines
    Lung
    Interferon Receptors
    Galactosylceramides
    Kidney
    Mucus
    Intraperitoneal Injections
    Eosinophils
    Allergens
    Fibrosis
    Epithelium
    Macrophages
    Inflammation
    Gene Expression
    Injections

    Keywords

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

    ASJC Scopus subject areas

    • Immunology
    • Immunology and Allergy

    Cite this

    Kudo, F., Ikutani, M., Seki, Y., Otsubo, T., Kawamura, Y. I., Dohi, T., ... Takaki, S. (2016). Interferon-γ constrains cytokine production of group 2 innate lymphoid cells. Immunology, 147(1), 21-29. https://doi.org/10.1111/imm.12537

    Interferon-γ constrains cytokine production of group 2 innate lymphoid cells. / Kudo, Fujimi; Ikutani, Masashi; Seki, Yoichi; Otsubo, Takeshi; Kawamura, Yuki I.; Dohi, Taeko; Oshima, Kenshiro; Hattori, Masahira; Nakae, Susumu; Takatsu, Kiyoshi; Takaki, Satoshi.

    In: Immunology, Vol. 147, No. 1, 01.01.2016, p. 21-29.

    Research output: Contribution to journalArticle

    Kudo, F, Ikutani, M, Seki, Y, Otsubo, T, Kawamura, YI, Dohi, T, Oshima, K, Hattori, M, Nakae, S, Takatsu, K & Takaki, S 2016, 'Interferon-γ constrains cytokine production of group 2 innate lymphoid cells', Immunology, vol. 147, no. 1, pp. 21-29. https://doi.org/10.1111/imm.12537
    Kudo F, Ikutani M, Seki Y, Otsubo T, Kawamura YI, Dohi T et al. Interferon-γ constrains cytokine production of group 2 innate lymphoid cells. Immunology. 2016 Jan 1;147(1):21-29. https://doi.org/10.1111/imm.12537
    Kudo, Fujimi ; Ikutani, Masashi ; Seki, Yoichi ; Otsubo, Takeshi ; Kawamura, Yuki I. ; Dohi, Taeko ; Oshima, Kenshiro ; Hattori, Masahira ; Nakae, Susumu ; Takatsu, Kiyoshi ; Takaki, Satoshi. / Interferon-γ constrains cytokine production of group 2 innate lymphoid cells. In: Immunology. 2016 ; Vol. 147, No. 1. pp. 21-29.
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