Signal Inhibitory Receptor on Leukocytes-1 recognizes S100 proteins

Rumpret, M.; von Richthofen, H. J.; van der Linden, M.; Westerlaken, G. H. A.; Talavera Ormeno, C.; Low, T. Y.; Ovaa, H.; Meyaard, L.

doi:10.1101/2021.05.14.444196

bioRxiv · 10.1101/2021.05.14.444196

Signal Inhibitory Receptor on Leukocytes-1 recognizes S100 proteins

Rumpret, M.·von Richthofen, H. J.·van der Linden, M.·Westerlaken, G. H. A.·Talavera Ormeno, C.·Low, T. Y.·Ovaa, H.·Meyaard, L.

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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.

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Rumpret, M., von Richthofen, H. J., van der Linden, M., Westerlaken, G. H. A., Talavera Ormeno, C., Low, T. Y., Ovaa, H., Meyaard, L.. 2021-05-16. Signal Inhibitory Receptor on Leukocytes-1 recognizes S100 proteins. https://doi.org/10.1101/2021.05.14.444196

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