PVNOXT regulates acinar cell-mediated inflammatory response via DMVACh projections to the acinar cell

  • J Neuroinflammation. 2026 May 25. doi: 10.1186/s12974-026-03870-8.
Hui Fang  #  1  2 ,  An Liu  #  1 ,  Jun-Fa Yang  #  3 ,  Min Liu  1  2 ,  Yin-Ying Zheng  1  2 ,  Hong-Yan Zhang  1 ,  Jin-Rong Guo  1 ,  Piao-Piao Luo  1 ,  Da-Shuai Yang  4 ,  Rui Wang  1  2 ,  Fu Lai  1  2 ,  Qiu-Ping Chen  1  2 ,  Tao Xu  4 ,  Hua Wang  5  6 ,  Zhen-Hua Ren  7  8
Affiliations
  • 1. School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, Anhui, China.
  • 2. Anhui Provincial Key Laboratory for Brain Bank Construction and Resource Utilization, Hefei, 230032, Anhui, China.
  • 3. Department of Emergency Surgery, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230032, Anhui, China.
  • 4. Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, 230032, Anhui, China.
  • 5. Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, 230032, Anhui, China. [email protected].
  • 6. Department of Oncology, the First Affiliated Hospital of Anhui Medical University, Hefei, 230032, Anhui, China. [email protected].
  • 7. School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, Anhui, China. [email protected].
  • 8. Anhui Provincial Key Laboratory for Brain Bank Construction and Resource Utilization, Hefei, 230032, Anhui, China. [email protected].
  • # Contributed equally.
PMID: 42186091 DOI: 10.1186/s12974-026-03870-8
Abstract

The central nervous system regulates glandular secretions by modulating visceral organ functions. However, the anatomical and functional connections between the brain and digestive enzyme-producing pancreatic acinar cells remain poorly defined. Using the hypertriglyceridemia-associated acute pancreatitis (HTGP) mouse model, we aimed to describe a functional transneuronal circuit connecting the hypothalamus to pancreatic acinar cells in mice. This circuit originates from a subpopulation of oxytocin neurons in the paraventricular hypothalamic nucleus (PVNOXT), and reaches the exocrine pancreas via acetylcholinergic neurons in the dorsal motor nucleus of the vagus (DMVACh) to innervate acinar cells. Silencing of PVNOXT neurons suppresses digestive enzyme secretion and inhibits the inflammatory response in HTGP. Conversely, stimulation of these neurons induces inflammation by dysregulating secretory pathways in acinar cells. Single-cell RNA Sequencing revealed that WD repeat and FYVE domain-containing 1 (Wdfy1), a gene expressed in the OXT neuron subpopulation, plays a critical role in the acinar cell-mediated inflammatory response, and its function is essential for the PVNOXT-DMVACh axis.

Keywords
Acinar cells; Functional transneuronal circuit; Inflammatory response; Pancreas.
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