J Immunol. 2026 Nov 2;215(11):vkag304. doi: 10.1093/jimmun/vkag304.
ABSTRACT
Interleukin-1 beta (IL-1β) is a highly proinflammatory cytokine whose synthesis and cleavage are tightly regulated. It is important for protection from several infections, but can also play a damaging role in autoimmune and autoinflammatory diseases. While pattern recognition receptor activation leads to potent induction of IL-1β, its production at steady state and the nature of cells that make IL-1β in vivo is not fully understood. Therefore, tools to detect early transcription of IL-1β-producing cells and permanent labeling of the lineage can provide critical insights into the functioning of the innate immune system. Here, we describe a novel IGNITE (IL-1β-Guided Neon green with Irreversible tdTomato Expression) mouse, a dual-reporter model that enables real-time visualization of Il1b transcription via mNeonGreen and permanent lineage tracing through Cre-dependent tdTomato expression. Using this system, we tracked Il1b-associated mNeonGreen and subsequent tdTomato expression both in vitro and in vivo. Unexpectedly, we identified heterogeneous tdTomato cell populations across multiple tissues in unmanipulated IGNITE mice, suggesting that a subset of myeloid cells transcribes Il1b at homeostasis without needing an experimentally driven activation of pattern recognition receptors. Neutrophils, monocytes, macrophages, and dendritic cells had different tdTomato+ proportions, suggesting varied encounters with inflammatory stimuli. Transcriptomic analysis revealed an unexpected dichotomy in the induction of NF-κB- versus IRF-mediated genes between tdTomato+ and tdTomato- conventional dendritic cell type 2 populations, following Toll-like receptor stimulation. Thus, the IGNITE mouse provides a powerful new tool for studying Il1b transcriptional dynamics and fate mapping, offering new insights into the spatial and temporal regulation of innate immune responses.
PMID:43020121 | DOI:10.1093/jimmun/vkag304