Decoding IL-1 receptor 1 and 2 expression profiles across organs in sepsis

CHUYI TAN^1*Weiqin Wang¹Han Ma¹Huan Chen¹Huali Zhang¹Yue Pen²Yiying Yang¹

• ¹Central South University Xiangya School of Medicine, Changsha, China
• ²Third Xiangya Hospital of Central South University, Changsha, China

Interleukin-1 (IL-1), a central inflammatory mediator, plays a critical role in sepsis. IL-1 signals through the IL-1 receptor families, including the signaling receptor IL-1R1 and the decoy receptor IL-1R2. But their cell-type-specific and organ-specific expression dynamics during sepsis remain poorly understood. Using single-cell RNA sequencing and flow cytometry, we investigated the expression patterns of IL-1R1 and IL-1R2 in murine lung, liver, heart, and intestine during sepsis. We found that IL-1R1 was predominantly expressed on non-immune cells (lung fibroblasts, liver endothelial cells and heart fibroblasts), and showed increased changes during sepsis. In contrast, IL-1R2 was primarily expressed on neutrophils and monocyte-derived macrophages in healthy conditions, with minimal expression on tissue resident macrophages (like such as alveolar macrophages, and Kupffer cells ). Sepsis induced a significant upregulation of IL-1R2 on neutrophils and monocyte-derived macrophages across all organs. However, resident macrophages in the lung, liver and heart maintain low expression during sepsis. These findings offer a deep understanding of IL-1 receptors biology and shed light on their contributions to immune modulation and tissue-specific responses in sepsis.