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Fibroblastic reticular cells in lymph node potentiate white adipose tissue beiging through neuro-immune crosstalk in male mice

Author

Listed:
  • Lai Yee Cheong

    (The University of Hong Kong
    The University of Hong Kong)

  • Baile Wang

    (The University of Hong Kong
    The University of Hong Kong)

  • Qin Wang

    (The University of Hong Kong
    The University of Hong Kong)

  • Leigang Jin

    (The University of Hong Kong
    The University of Hong Kong)

  • Kelvin H. M. Kwok

    (The University of Hong Kong
    The University of Hong Kong)

  • Xiaoping Wu

    (The University of Hong Kong
    The University of Hong Kong)

  • Lingling Shu

    (The University of Hong Kong
    The University of Hong Kong)

  • Huige Lin

    (The Hong Kong Polytechnic University)

  • Sookja Kim Chung

    (The University of Hong Kong
    Macau University of Science and Technology)

  • Kenneth K. Y. Cheng

    (The Hong Kong Polytechnic University)

  • Ruby L. C. Hoo

    (The University of Hong Kong
    The University of Hong Kong)

  • Aimin Xu

    (The University of Hong Kong
    The University of Hong Kong
    The University of Hong Kong)

Abstract

Lymph nodes (LNs) are always embedded in the metabolically-active white adipose tissue (WAT), whereas their functional relationship remains obscure. Here, we identify fibroblastic reticular cells (FRCs) in inguinal LNs (iLNs) as a major source of IL-33 in mediating cold-induced beiging and thermogenesis of subcutaneous WAT (scWAT). Depletion of iLNs in male mice results in defective cold-induced beiging of scWAT. Mechanistically, cold-enhanced sympathetic outflow to iLNs activates β1- and β2-adrenergic receptor (AR) signaling in FRCs to facilitate IL-33 release into iLN-surrounding scWAT, where IL-33 activates type 2 immune response to potentiate biogenesis of beige adipocytes. Cold-induced beiging of scWAT is abrogated by selective ablation of IL-33 or β1- and β2-AR in FRCs, or sympathetic denervation of iLNs, whereas replenishment of IL-33 reverses the impaired cold-induced beiging in iLN-deficient mice. Taken together, our study uncovers an unexpected role of FRCs in iLNs in mediating neuro-immune interaction to maintain energy homeostasis.

Suggested Citation

  • Lai Yee Cheong & Baile Wang & Qin Wang & Leigang Jin & Kelvin H. M. Kwok & Xiaoping Wu & Lingling Shu & Huige Lin & Sookja Kim Chung & Kenneth K. Y. Cheng & Ruby L. C. Hoo & Aimin Xu, 2023. "Fibroblastic reticular cells in lymph node potentiate white adipose tissue beiging through neuro-immune crosstalk in male mice," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36737-0
    DOI: 10.1038/s41467-023-36737-0
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    References listed on IDEAS

    as
    1. Yong Chen & Kenji Ikeda & Takeshi Yoneshiro & Annarita Scaramozza & Kazuki Tajima & Qiang Wang & Kyeongkyu Kim & Kosaku Shinoda & Carlos Henrique Sponton & Zachary Brown & Andrew Brack & Shingo Kajimu, 2019. "Thermal stress induces glycolytic beige fat formation via a myogenic state," Nature, Nature, vol. 565(7738), pages 180-185, January.
    2. Vanessa Pellegrinelli & Vivian J. Peirce & Laura Howard & Samuel Virtue & Dénes Türei & Martina Senzacqua & Andrea Frontini & Jeffrey W. Dalley & Antony R. Horton & Guillaume Bidault & Ilenia Severi &, 2018. "Adipocyte-secreted BMP8b mediates adrenergic-induced remodeling of the neuro-vascular network in adipose tissue," Nature Communications, Nature, vol. 9(1), pages 1-18, December.
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