Salient type 1 interleukin 1 receptor expression in peripheral non-immune cells.

Area of Science:

• Immunology
• Cell Biology
• Molecular Biology

Background:

• Interleukin 1 (IL-1) is a key cytokine mediating inflammation and immunity via its receptor, type I interleukin 1 receptor (IL-1R1).
• Previous research primarily focused on IL-1R1 expression in immune cells, leaving its distribution in other peripheral tissues less understood.

Purpose of the Study:

• To comprehensively map the distribution of IL-1R1 in various peripheral tissues.
• To identify novel cell types expressing IL-1R1 and elucidate their role in IL-1 signaling.

Main Methods:

• Utilized IL-1R1 reporter (IL-1R1GR/GR) mice for highly sensitive in situ detection of IL-1R1 mRNA and protein.
• Performed detailed tissue analysis across multiple peripheral organs.
• Conducted functional assays on spleen fibroblastic reticular cells (FRCs) to assess their response to IL-1β stimulation.

Main Results:

• Confirmed IL-1R1 expression in endocrine tissues (pituitary, pancreas).
• Refuted exclusive neuronal expression in spinal cord dorsal horn and dorsal root ganglia (DRG); identified IL-1R1 in endothelial cells within DRG, spinal cord, pancreas, colon, muscles, and immune organs.
• Discovered high IL-1R1 expression in gp38+ fibroblastic reticular cells (FRCs) in the colon and immune organs, rather than tissue macrophages.
• Demonstrated rapid in vivo response of spleen FRCs to systemic IL-1β stimulation.

Conclusions:

• Provides a rigorous re-examination of IL-1R1 expression patterns in peripheral tissues.
• Identifies endothelial cells as a significant site of IL-1R1 expression in the periphery.
• Reveals tissue FRCs as a novel, previously unappreciated cell type with high IL-1R1 expression, playing a crucial role in peripheral IL-1 signaling.