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Adipose group 1 innate lymphoid cells promote adipose tissue fibrosis and diabetes in obesity

Author

Listed:
  • Hongdong Wang

    (Drum Tower Hospital Affiliated to Nanjing University Medical School)

  • Lei Shen

    (Shanghai Jiao Tong University School of Medicine)

  • Xitai Sun

    (Drum Tower Hospital Affiliated to Nanjing University Medical School)

  • Fangcen Liu

    (Drum Tower Hospital Clinical College of Nanjing Medical University)

  • Wenhuan Feng

    (Drum Tower Hospital Affiliated to Nanjing University Medical School)

  • Chunping Jiang

    (Drum Tower Hospital Affiliated to Nanjing University Medical School)

  • Xuehui Chu

    (Drum Tower Hospital Affiliated to Nanjing University Medical School)

  • Xiao Ye

    (Drum Tower Hospital Clinical College of Nanjing Medical University)

  • Can Jiang

    (Drum Tower Hospital Affiliated to Nanjing University Medical School)

  • Yan Wang

    (Drum Tower Hospital Affiliated to Nanjing University Medical School)

  • Pengzi Zhang

    (Drum Tower Hospital Affiliated to Nanjing University Medical School)

  • Mengwei Zang

    (University of Texas Health San Antonio)

  • Dalong Zhu

    (Drum Tower Hospital Affiliated to Nanjing University Medical School)

  • Yan Bi

    (Drum Tower Hospital Affiliated to Nanjing University Medical School)

Abstract

Pathogenic factors driving obesity to type 2 diabetes (T2D) are not fully understood. Group 1 innate lymphoid cells (ILC1s) are effectors of innate immunity and enriched in inflamed tissues. Here we show that the number of adipose ILC1s increases in obese T2D patients and correlates with glycemic parameters and with the number of ILC1s in the blood; circulating ILC1 numbers decrease as a result of metabolic improvements after bariatric surgery. In vitro co-culture experiments show that human adipose ILC1s promote adipose fibrogenesis and CD11c+ macrophage activation. Reconstruction of the adipose ILC1 population in Prkdc−/−IL2rg−/− mice by adoptive transfer drives adipose fibrogenesis through activation of TGFβ1 signaling; however, transfer of Ifng−/− ILC1s has no effect on adipose fibrogenesis. Furthermore, inhibiting adipose accumulation of ILC1s using IL-12 neutralizing antibodies attenuates adipose tissue fibrosis and improves glycemic tolerance. Our data present insights into the mechanisms of local immune disturbances in obesity-related T2D.

Suggested Citation

  • Hongdong Wang & Lei Shen & Xitai Sun & Fangcen Liu & Wenhuan Feng & Chunping Jiang & Xuehui Chu & Xiao Ye & Can Jiang & Yan Wang & Pengzi Zhang & Mengwei Zang & Dalong Zhu & Yan Bi, 2019. "Adipose group 1 innate lymphoid cells promote adipose tissue fibrosis and diabetes in obesity," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11270-1
    DOI: 10.1038/s41467-019-11270-1
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    Cited by:

    1. Yichao Lu & Zhenyu Luo & Huanli Zhou & Yingying Shi & Ying Zhu & Xuemeng Guo & Jiaxin Huang & Junlei Zhang & Xu Liu & Sijie Wang & Xinyu Shan & Hang Yin & Yongzhong Du & Qingpo Li & Jian You & Lihua L, 2024. "A nanoemulsion targeting adipose hypertrophy and hyperplasia shows anti-obesity efficiency in female mice," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    2. Hongdong Wang & Yanhua Du & Shanshan Huang & Xitai Sun & Youqiong Ye & Haixiang Sun & Xuehui Chu & Xiaodong Shan & Yue Yuan & Lei Shen & Yan Bi, 2024. "Single-cell analysis reveals a subpopulation of adipose progenitor cells that impairs glucose homeostasis," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

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