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Stress-induced red nucleus attenuation induces anxiety-like behavior and lymph node CCL5 secretion

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Listed:
  • Dong-Dong Shi

    (Shanghai Jiao Tong University School of Medicine
    Shanghai Jiao Tong University School of Medicine)

  • Ying-Dan Zhang

    (Shanghai Jiao Tong University School of Medicine)

  • Sen Zhang

    (Shanghai Jiao Tong University School of Medicine)

  • Bing-Bing Liao

    (Shanghai Jiao Tong University School of Medicine)

  • Min-Yi Chu

    (Shanghai Jiao Tong University School of Medicine)

  • Shanshan Su

    (Shanghai Jiao Tong University School of Medicine)

  • Kaiming Zhuo

    (Shanghai Jiao Tong University School of Medicine)

  • Hao Hu

    (Shanghai Jiao Tong University School of Medicine)

  • Chen Zhang

    (Shanghai Jiao Tong University School of Medicine)

  • Zhen Wang

    (Shanghai Jiao Tong University School of Medicine
    Shanghai Jiao Tong University School of Medicine
    Shanghai Jiao Tong University)

Abstract

Previous studies have speculated that brain activity directly controls immune responses in lymphoid organs. However, the upstream brain regions that control lymphoid organs and how they interface with lymphoid organs to produce stress-induced anxiety-like behavior remain elusive. Using stressed human participants and rat models, we show that CCL5 levels are increased in stressed individuals compared to controls. Stress-inducible CCL5 is mainly produced from cervical lymph nodes (CLN). Retrograde tracing from CLN identifies glutamatergic neurons in the red nucleus (RN), the activities of which are tightly correlated with CCL5 levels and anxiety-like behavior in male rats. Ablation or chemogenetic inhibition of RN glutamatergic neurons increases anxiety levels and CCL5 expression in the serum and CLNs, whereas pharmacogenetic activation of these neurons reduces anxiety levels and CCL5 synthesis after restraint stress exposure. Chemogenetic inhibition of the projection from primary motor cortex to RN elicits anxiety-like behavior and CCL5 synthesis. This brain-lymph node axis provides insights into lymph node tissue as a stress-responsive endocrine organ.

Suggested Citation

  • Dong-Dong Shi & Ying-Dan Zhang & Sen Zhang & Bing-Bing Liao & Min-Yi Chu & Shanshan Su & Kaiming Zhuo & Hao Hu & Chen Zhang & Zhen Wang, 2023. "Stress-induced red nucleus attenuation induces anxiety-like behavior and lymph node CCL5 secretion," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42814-1
    DOI: 10.1038/s41467-023-42814-1
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    References listed on IDEAS

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