The pyruvate-GPR31 axis promotes transepithelial dendrite formation in human intestinal dendritic cells

• 成果类型: Article
• 署名作者: Oguro-Igashira, Eri; Murakami, Mari; Mori, Ryota; Kuwahara, Ryuichi; Kihara, Takako; Kohara, Masaharu; Fujiwara, Makoto; Motooka, Daisuke; Okuzaki, Daisuke; Arase, Mitsuru; Toyota, Hironobu; Peng, Siyun; Ogino, Takayuki; Kitabatake, Yasuji; Morii, Eiichi; Hirota, Seiichi; Ikeuchi, Hiroki; Umemoto, Eiji; Kumanogoh, Atsushi; Takeda, Kiyoshi
• 署名单位: University of Osaka; University of Osaka; University of Osaka; University of Osaka; Hyogo Medical University; Hyogo Medical University; University of Osaka; University of Osaka; University of Osaka; University of Osaka; University of Osaka; University of Osaka; University of Shizuoka; University of Osaka
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-13893
• DOI: 10.1073/pnas.2318767121
• 发表日期: 2024-10-29
• 关键词: rna-seq data; gut microbiota; protein; bacteria; inflammation; maturation; extension; antigens; cd8(+); subset

摘要

The intestinal lumen is rich in gut microbial metabolites that serve as signaling molecules for gut immune cells. G- protein- coupled receptors (GPCRs) sense metabolites and can act as key mediators that translate gut luminal signals into host immune responses. However, the impacts of gut microbe-GPCR interactions on human physiology have not been fully elucidated. Here, we show that GPR31, which is activated by the gut bacterial metabolite pyruvate, is specifically expressed on type 1 conventional dendritic cells (cDC1s) in the lamina propria of the human intestine. Using human induced pluripotent stem cell- derived cDC1s and a monolayer human gut organoid coculture system, we show that cDC1s extend their dendrites toward pyruvate on the luminal side, forming transepithelial dendrites (TED). Accordingly, GPR31 activation via pyruvate enhances the fundamental function of cDC1 by allowing efficient uptake of gut luminal antigens, such as dietary compounds and bacterial particles through TED formation. Our results highlight the role of GPCRs in tuning the human gut immune system according to local metabolic cues.