Prenatal electroacupuncture modulates maternal-fetal immune activation via a brain-to-splenic signal

  • Cell Rep. 2025 Nov 25;44(11):116576. doi: 10.1016/j.celrep.2025.116576.
Zhiqing Zhang  1 ,  Weipeng Lin  2 ,  Jinglan Yan  3 ,  Xiaotong Wang  4 ,  Jingya Wang  5 ,  Feixue Wang  3 ,  Teng He  3 ,  Jing Xu  5 ,  Yucen Xia  6 ,  Yongjun Chen  7
Affiliations
  • 1. Institute of Acupuncture and Moxibustion, Shandong University of Traditional Chinese Medicine, Jinan 250300, China; South China Research Center for Acupuncture and Moxibustion, Clinical Medical College of Acupuncture, Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou 510006, China; Acupuncture Research Team, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China; Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou 510120, China.
  • 2. Institute of Acupuncture and Moxibustion, Shandong University of Traditional Chinese Medicine, Jinan 250300, China; Chongqing Key Laboratory of Precision Optics, Chongqing Institute of East China Normal University, Chongqing 401120, China.
  • 3. Institute of Acupuncture and Moxibustion, Shandong University of Traditional Chinese Medicine, Jinan 250300, China.
  • 4. School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing 102488, China.
  • 5. South China Research Center for Acupuncture and Moxibustion, Clinical Medical College of Acupuncture, Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
  • 6. Institute of Acupuncture and Moxibustion, Shandong University of Traditional Chinese Medicine, Jinan 250300, China; Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250300, China. Electronic address: [email protected].
  • 7. Institute of Acupuncture and Moxibustion, Shandong University of Traditional Chinese Medicine, Jinan 250300, China; South China Research Center for Acupuncture and Moxibustion, Clinical Medical College of Acupuncture, Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou 510006, China; Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250300, China. Electronic address: [email protected].
PMID: 41259207 DOI: 10.1016/j.celrep.2025.116576
Abstract

Maternal immune activation (MIA) during pregnancy is a major risk factor for adverse obstetric outcomes and neurodevelopmental disorders in offspring; yet the underlying mechanisms and effective interventions are not well established. Here, we identify a pivotal role of α7nAChR (nicotinic acetylcholine receptor)-mediated activation in splenic macrophages, which triggers an interleukin-6-driven inflammatory cascade, affecting the disruption of maternal-fetal immune balance. This process contributes to miscarriage, diminished neonatal survival, and long-term neuropsychiatric deficits in adulthood. We further identified that the paraventricular nucleus-vagus-α7nAChR-spleen circuit is a central regulator for gestational neuroimmune homeostasis. Prenatal electroacupuncture stimulation (ES) modulates macrophage activation and immune equilibrium at the maternal-fetal interface by engaging these circuits, improving perinatal outcomes, and mitigating neurodevelopmental impairments in offspring. These findings position the brain-spleen axis as a promising therapeutic target and support prenatal ES as a viable non-pharmacological strategy for preventing MIA-related complications.

Keywords
CP: immunology; CP: neuroscience research topic; electroacupuncture; macrophage; maternal immune activation; schizophrenia; vagus nerve.
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