2. Academic Validation
  3. Induced pluripotent stem cell-derived macrophages enable broad modeling of human inflammasome signaling

Induced pluripotent stem cell-derived macrophages enable broad modeling of human inflammasome signaling

  • Cell Rep Methods. 2026 Jun 25:101506. doi: 10.1016/j.crmeth.2026.101506.
Chloe M McKee 1,  Melanie Cranston 1,  Emma C McKay 2,  Mohammad Arefian 3,  Thea J Mawhinney 1,  Ben C Collins 3,  Rebecca C Coll 4
Affiliations

Affiliations

  • 1 Wellcome-Wolfson Institute for Experimental Medicine, Queen's University of Belfast, Belfast, UK.
  • 2 Wellcome-Wolfson Institute for Experimental Medicine, Queen's University of Belfast, Belfast, UK; School of Biological Sciences, Queen's University of Belfast, Belfast, UK.
  • 3 School of Biological Sciences, Queen's University of Belfast, Belfast, UK.
  • 4 Wellcome-Wolfson Institute for Experimental Medicine, Queen's University of Belfast, Belfast, UK. Electronic address: [email protected].
PMID: 42349410 DOI: 10.1016/j.crmeth.2026.101506
Abstract

Macrophage models are a mainstay of inflammasome research; however, current in vitro models have significant limitations. Here, we generate induced pluripotent stem cell (iPSC)-derived macrophages (iMacs) to study inflammasome signaling and benchmark them with human monocyte-derived macrophages. We confirm that iMacs express high levels of macrophage markers and are highly phagocytic. Proteomic analysis shows iMacs express many inflammasome sensors and related proteins, and iMacs respond to multiple inflammasome stimuli. The NLRP3 inflammasome is strongly activated in iMacs, and nigericin alone activates NLRP3. The non-canonical inflammasome does not require a priming step, and high NAIP/NLRC4 activation is observed in response to needle toxin. Finally, unlike human monocyte-derived macrophages (HMDMs), talabostat activates NLRP1 in iMacs. Therefore, we demonstrate that iMacs are a physiologically relevant and attractive model to study inflammasome signaling.

Keywords

CP: immunology; CP: stem cell; IL-1β; NLRC4; NLRP1; NLRP3; caspase-4; induced pluripotent stem cells; inflammasomes; inflammation; innate immunity; macrophages.

Figures
Products