A type 2 immune circuit in the stomach controls mammalian adaptation to dietary chitin

• 成果类型: Article
• 署名作者: Kim, Do-Hyun; Wang, Yilin; Jung, Haerin; Field, Rachael L.; Zhang, Xinya; Liu, Ta-Chiang; Ma, Changqing; Fraser, James S.; Brestoff, Jonathan R.; Van Dyken, Steven J.
• 署名单位: Washington University (WUSTL); University of California System; University of California San Francisco
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-10830
• DOI: 10.1126/science.add5649
• 发表日期: 2023-09-08
• 页码: 1092-1097
• 关键词: innate lymphoid-cells; tissue; accumulation; eosinophils; activation; EVOLUTION; responses; triggers; distinct; obesity

摘要

Dietary fiber improves metabolic health, but host-encoded mechanisms for digesting fibrous polysaccharides are unclear. In this work, we describe a mammalian adaptation to dietary chitin that is coordinated by gastric innate immune activation and acidic mammalian chitinase (AMCase). Chitin consumption causes gastric distension and cytokine production by stomach tuft cells and group 2 innate lymphoid cells (ILC2s) in mice, which drives the expansion of AMCase-expressing zymogenic chief cells that facilitate chitin digestion. Although chitin influences gut microbial composition, ILC2-mediated tissue adaptation and gastrointestinal responses are preserved in germ-free mice. In the absence of AMCase, sustained chitin intake leads to heightened basal type 2 immunity, reduced adiposity, and resistance to obesity. These data define an endogenous metabolic circuit that enables nutrient extraction from an insoluble dietary constituent by enhancing digestive function.