2025-11-11 東京大学,京都大学,東京科学大学
図1:ヒト単球のIL-1β放出の瞬間
LCI-Sによって撮影したヒト単球が炎症性細胞死(パイロトーシス)に伴って炎症性サイトカインIL-1βを放出する様子。上:明視野+細胞死染色SYTOX orange(ピンク)、下:IL-1β放出(Green-Fire-Blue)。撮影間隔はおよそ1時間ごと。
<関連情報>
- https://www.rcast.u-tokyo.ac.jp/ja/news/release/20251111.html
- https://www.nature.com/articles/s41590-025-02319-z
単一細胞解析により、ヒト単球におけるNLRP3を介したIL-1β分泌の駆動力として細胞死が明らかになった Single-cell analysis reveals cell death as driver of NLRP3-mediated secretion of IL-1β in human monocytes
Lieselotte Vande Walle,Kentaro Kato,Mai Yamagishi,Takashi Kamatani,Alex Vervaeke,Rosa Martín-Pérez,Masaki Shimizu,Takumi Takizawa,Junko Takita,Ryuta Nishikomori,Osamu Ohara,Kazushi Izawa,Yoshitaka Shirasaki & Mohamed Lamkanfi
Nature Immunology Published:11 November 2025
DOI:https://doi.org/10.1038/s41590-025-02319-z
Abstract
Interleukin-1β (IL-1β) is a key proinflammatory cytokine with critical roles in infections and inflammatory diseases, yet the mechanisms regulating its release from human monocytes remain unclear. Here we used a suite of single-cell approaches, including integrated live-cell imaging of secretion and cell fate, flow cytometry and high-content imaging, to investigate IL-1β secretion dynamics in lipopolysaccharide-stimulated primary human peripheral blood CD14+ monocytes. We found marked heterogeneity: a large fraction of cells remained viable and contributed negligibly to IL-1β secretion, challenging established models. Instead, a small subset (5–10%) undergoing canonical NLRP3 inflammasome activation and GSDMD-dependent pyroptosis produced the majority of secreted IL-1β, with a smaller contribution from apoptotic cells transitioning to secondary necrosis. Single-cell profiling of CD14+ monocytes from patients with cryopyrin-associated periodic syndrome confirmed lytic cell death as the driver of pathological IL-1β release. These findings redefine IL-1β as a damage-associated molecular pattern, secreted predominantly by dying monocytes.
