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

Area of Science:

• Immunology
• Cell Biology
• Sepsis Pathogenesis

Background:

• Interleukin-1 (IL-1) is a critical mediator in sepsis pathogenesis.
• IL-1 signaling occurs via IL-1R1 and IL-1R2, but their organ- and cell-specific expression during sepsis is not well understood.

Purpose of the Study:

• To systematically analyze the cell-type and organ-specific expression of IL-1R1 and IL-1R2 during sepsis.
• To elucidate the role of IL-1 receptors in immune modulation and tissue-specific responses in sepsis.

Main Methods:

• Utilized single-cell RNA sequencing (scRNA-seq) datasets.
• Validated findings using flow cytometry in murine models of cecal ligation and puncture (CLP)-induced sepsis.
• Examined expression across lung, liver, heart, and small intestine.

Main Results:

• IL-1R1 is mainly on non-immune cells and increases during sepsis.
• IL-1R2 is primarily on neutrophils and monocyte-derived macrophages, with sepsis upregulating it on these cells.
• Resident macrophages in multiple organs maintain low IL-1R2 expression during sepsis.

Conclusions:

• Distinct and compartmentalized expression landscapes for IL-1R1 and IL-1R2 exist across organs during sepsis.
• Findings enhance understanding of IL-1 receptor biology in sepsis.
• Provides insights into immune modulation and tissue-specific responses in sepsis.