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Costimulation of type-2 innate lymphoid cells by GITR promotes effector function and ameliorates type 2 diabetes

Author

Listed:
  • Lauriane Galle-Treger

    (University of Southern California)

  • Ishwarya Sankaranarayanan

    (University of Southern California)

  • Benjamin P. Hurrell

    (University of Southern California)

  • Emily Howard

    (University of Southern California)

  • Richard Lo

    (University of Southern California)

  • Hadi Maazi

    (University of Southern California)

  • Gavin Lewis

    (Janssen Research and Development)

  • Homayon Banie

    (Janssen Research and Development)

  • Alan L. Epstein

    (University of Southern California)

  • Peisheng Hu

    (University of Southern California)

  • Virender K. Rehan

    (Harbor-UCLA Medical Center)

  • Frank D. Gilliland

    (University of Southern California)

  • Hooman Allayee

    (University of Southern California)

  • Pejman Soroosh

    (Janssen Research and Development)

  • Arlene H. Sharpe

    (Harvard Medical School)

  • Omid Akbari

    (University of Southern California)

Abstract

Metabolic syndrome is characterized by disturbances in glucose homeostasis and the development of low-grade systemic inflammation, which increase the risk to develop type 2 diabetes mellitus (T2DM). Type-2 innate lymphoid cells (ILC2s) are a recently discovered immune population secreting Th2 cytokines. While previous studies show how ILC2s can play a critical role in the regulation of metabolic homeostasis in the adipose tissue, a therapeutic target capable of modulating ILC2 activation has yet to be identified. Here, we show that GITR, a member of the TNF superfamily, is expressed on both murine and human ILC2s. Strikingly, we demonstrate that GITR engagement of activated, but not naïve, ILC2s improves glucose homeostasis, resulting in both protection against insulin resistance onset and amelioration of established insulin- resistance. Together, these results highlight the critical role of GITR as a novel therapeutic molecule against T2DM and its fundamental role as an immune checkpoint for activated ILC2s.

Suggested Citation

  • Lauriane Galle-Treger & Ishwarya Sankaranarayanan & Benjamin P. Hurrell & Emily Howard & Richard Lo & Hadi Maazi & Gavin Lewis & Homayon Banie & Alan L. Epstein & Peisheng Hu & Virender K. Rehan & Fra, 2019. "Costimulation of type-2 innate lymphoid cells by GITR promotes effector function and ameliorates type 2 diabetes," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-08449-x
    DOI: 10.1038/s41467-019-08449-x
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    Cited by:

    1. Lauriane Galle-Treger & Doumet Georges Helou & Christine Quach & Emily Howard & Benjamin P. Hurrell & German R. Aleman Muench & Pedram Shafiei-Jahani & Jacob D. Painter & Andrea Iorga & Lily Dara & Ju, 2022. "Autophagy impairment in liver CD11c+ cells promotes non-alcoholic fatty liver disease through production of IL-23," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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