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Autophagy impairment in liver CD11c+ cells promotes non-alcoholic fatty liver disease through production of IL-23

Author

Listed:
  • Lauriane Galle-Treger

    (University of Southern California)

  • Doumet Georges Helou

    (University of Southern California)

  • Christine Quach

    (University of Southern California)

  • Emily Howard

    (University of Southern California)

  • Benjamin P. Hurrell

    (University of Southern California)

  • German R. Aleman Muench

    (Janssen Research and Development)

  • Pedram Shafiei-Jahani

    (University of Southern California)

  • Jacob D. Painter

    (University of Southern California)

  • Andrea Iorga

    (University of Southern California
    University of Southern California)

  • Lily Dara

    (University of Southern California
    University of Southern California)

  • Juliet Emamaullee

    (University of Southern California)

  • Lucy Golden-Mason

    (University of Southern California
    University of Southern California
    University of Southern California)

  • Hugo R. Rosen

    (University of Southern California
    University of Southern California
    University of Southern California)

  • Pejman Soroosh

    (Janssen Research and Development)

  • Omid Akbari

    (University of Southern California
    University of Southern California)

Abstract

There has been a global increase in rates of obesity with a parallel epidemic of non-alcoholic fatty liver disease (NAFLD). Autophagy is an essential mechanism involved in the degradation of cellular material and has an important function in the maintenance of liver homeostasis. Here, we explore the effect of Autophagy-related 5 (Atg5) deficiency in liver CD11c+ cells in mice fed HFD. When compared to control mice, Atg5-deficient CD11c+ mice exhibit increased glucose intolerance and decreased insulin sensitivity when fed HFD. This phenotype is associated with the development of NAFLD. We observe that IL-23 secretion is induced in hepatic CD11c+ myeloid cells following HFD feeding. We demonstrate that both therapeutic and preventative IL-23 blockade alleviates glucose intolerance, insulin resistance and protects against NAFLD development. This study provides insights into the function of autophagy and IL-23 production by hepatic CD11c+ cells in NAFLD pathogenesis and suggests potential therapeutic targets.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29174-y
    DOI: 10.1038/s41467-022-29174-y
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    References listed on IDEAS

    as
    1. 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.
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    4. Doumet Georges Helou & Pedram Shafiei-Jahani & Richard Lo & Emily Howard & Benjamin P. Hurrell & Lauriane Galle-Treger & Jacob D. Painter & Gavin Lewis & Pejman Soroosh & Arlene H. Sharpe & Omid Akbar, 2020. "PD-1 pathway regulates ILC2 metabolism and PD-1 agonist treatment ameliorates airway hyperreactivity," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
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