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

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 and Aimin Xu ()
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Lai Yee Cheong: The University of Hong Kong
Baile Wang: The University of Hong Kong
Qin Wang: The University of Hong Kong
Leigang Jin: The University of Hong Kong
Kelvin H. M. Kwok: The University of Hong Kong
Xiaoping Wu: The University of Hong Kong
Lingling Shu: The University of Hong Kong
Huige Lin: The Hong Kong Polytechnic University
Sookja Kim Chung: The University of Hong Kong
Kenneth K. Y. Cheng: The Hong Kong Polytechnic University
Ruby L. C. Hoo: The University of Hong Kong
Aimin Xu: The University of Hong Kong

Nature Communications, 2023, vol. 14, issue 1, 1-18

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-36737-0

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