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<p>Neuroimmune signals can regulate neuronal function and affect behavior through mechanisms that are not yet fully understood. Here we investigated the action of interleukin 13 (IL-13), a cytokine that can be produced in the brain by both microglia and neurons. We show that dopamine-containing neurons in the ventral tegmental area (VTA) predominantly express the IL-13 receptor alpha 1 (IL-13Rα1) and exhibit presynaptic vesicular localization of neuronal IL-13. Exogenous application of IL-13, or its endogenous mobilization by optogenetics, reduced the activity of VTA dopaminergic neurons and opposed the stimulatory effects of nicotine on these neurons in rodents. These actions required IL-13Rα1, activation of the PI3K/AKT pathway, and functional hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. Consistently, local infusion of IL-13 into the VTA markedly reduced nicotine self-administration in rodents. Collectively, these findings demonstrate that IL-13 acts in a neuromodulator-like fashion on mesolimbic dopamine neurons expressing IL-13Rα1. Our data also indicate that IL-13Rα1 signaling regulates the stimulatory actions of nicotine, suggesting a potential role for this neuronal immune signaling in reward processing and the addictive properties of nicotine.</p><p></p>

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Interleukin 13 signaling modulates dopaminergic functions and nicotine reward in rodents

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月7日

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  • Xin-an Liu,
  • Carlos A. Aguirre,
  • Qixing Yang,
  • Jiayan Ren,
  • Lina Wang,
  • Furong Ju,
  • Hongling Guo,
  • Jintao Wang,
  • Luping Liu,
  • Zixuan Li,
  • Juan He,
  • Zhibin Xu,
  • Cuihan Shi,
  • Rigo Cintron-Colon,
  • Tatiana Michel,
  • Malcolm Wood,
  • Alexander V. Margetts,
  • Tate A. Pollock,
  • Samara J. Vilca,
  • Luis M. Tuesta,
  • Silvia Di Angelantonio,
  • Bernadette Basilico,
  • Maria Egle De Stefano,
  • Jianxun Xia,
  • Pengfei Wei,
  • Shupeng Li,
  • Xiaofei Yang,
  • Liping Wang,
  • Violaine D. Delorme-Walker,
  • Maria Cecillia Garibaldi Marcondes,
  • Loren Parsons,
  • Bruno Conti,
  • Zuxin Chen

摘要

Neuroimmune signals can regulate neuronal function and affect behavior through mechanisms that are not yet fully understood. Here we investigated the action of interleukin 13 (IL-13), a cytokine that can be produced in the brain by both microglia and neurons. We show that dopamine-containing neurons in the ventral tegmental area (VTA) predominantly express the IL-13 receptor alpha 1 (IL-13Rα1) and exhibit presynaptic vesicular localization of neuronal IL-13. Exogenous application of IL-13, or its endogenous mobilization by optogenetics, reduced the activity of VTA dopaminergic neurons and opposed the stimulatory effects of nicotine on these neurons in rodents. These actions required IL-13Rα1, activation of the PI3K/AKT pathway, and functional hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. Consistently, local infusion of IL-13 into the VTA markedly reduced nicotine self-administration in rodents. Collectively, these findings demonstrate that IL-13 acts in a neuromodulator-like fashion on mesolimbic dopamine neurons expressing IL-13Rα1. Our data also indicate that IL-13Rα1 signaling regulates the stimulatory actions of nicotine, suggesting a potential role for this neuronal immune signaling in reward processing and the addictive properties of nicotine.