Abstract
Signal inhibitory receptor on leukocytes-1 (SIRL-1) is an inhibitory receptor with a hitherto unknown ligand, and is expressed on human monocytes and neutrophils. SIRL-1 inhibits myeloid effector functions such as reactive oxygen species (ROS) production. We here identify S100 proteins as SIRL-1 ligands. S100 proteins are composed of two calcium-binding domains. Various S100 proteins are damage-associated molecular patterns (DAMPs) released from damaged cells, after which they initiate inflammation by ligating activating receptors on immune cells. We now show that the inhibitory SIRL-1 recognizes individual calcium-binding domains of all tested S100 proteins. Blocking SIRL-1 on human neutrophils enhanced S100 protein S100A6-induced ROS production, showing that S100A6 suppresses neutrophil ROS production via SIRL-1. We conclude that SIRL-1 is an inhibitory receptor recognizing the S100 protein family of DAMPs.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
↵† Deceased
Abbreviations
- SIRL-1
- Signal inhibitory receptor on leukocytes-1
- LAIR-1
- Leukocyte-associated immunoglobulin-like receptor-1
- ROS
- reactive oxygen species;
- DAMP
- damage-associated molecular pattern;
- MS
- mass spectrometry;
- FBS
- fetal bovine serum;
- Fmoc
- 9-fluoronylmethoxycarbonyl