Neuronal-ILC2 interactions regulate pancreatic glucagon and glucose homeostasis

• 成果类型: Article
• 署名作者: Sestan, Marko -; Raposo, Bruno; Rendas, Miguel; Brea, David; Pirzgalska, Roksana; Rasteiro, Ana; Aliseychik, Maria; Godinho, Ines; Ribeiro, Helder; Carvalho, Tania; Wueest, Stephan; Konrad, Daniel; Veiga-Fernandes, Henrique
• 署名单位: University of Rijeka; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto de Investigaciones Biomedicas de Barcelona (IIBB); University of Zurich; University Children's Hospital Zurich; University Children's Hospital Zurich; University of Zurich; University of Zurich; Zurich Center Integrative Human Physiology (ZIHP)
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-13794
• DOI: 10.1126/science.adi3624
• 发表日期: 2025-01-17
• 页码: 261-+
• 关键词: innate lymphoid-cells; neuroimmune circuits; insulin-secretion; mice; expression; neurons; immune

摘要

The immune system shapes body metabolism, while interactions between peripheral neurons and immune cells control tissue homeostasis and immunity. However, whether peripheral neuroimmune interactions orchestrate endocrine system functions remains unexplored. After fasting, mice lacking type 2 innate lymphoid cells (ILC2s) displayed disrupted glucose homeostasis, impaired pancreatic glucagon secretion, and inefficient hepatic gluconeogenesis. Additionally, intestinal ILC2s were found in the pancreas, which was dependent on their expression of the adrenergic beta 2 receptor. Targeted activation of catecholaminergic intestinal neurons promoted the accumulation of ILC2s in the pancreas. Our work provides evidence that immune cells can be regulated by neuronal signals in response to fasting, activating an inter-organ communication route that promotes pancreatic endocrine function and regulation of blood glucose levels.