TY - JOUR
T1 - Recognition of S100 proteins by Signal Inhibitory Receptor on Leukocytes-1 negatively regulates human neutrophils
AU - Rumpret, Matevž
AU - von Richthofen, Helen J.
AU - van der Linden, Maarten
AU - Westerlaken, Geertje H.A.
AU - Talavera Ormeño, Cami
AU - Low, Teck Y.
AU - Ovaa, Huib
AU - Meyaard, Linde
N1 - Publisher Copyright:
© 2021 The Authors. European Journal of Immunology published by Wiley-VCH GmbH
PY - 2021/9
Y1 - 2021/9
N2 - 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. In this study, we 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. Taken together, SIRL-1 is an inhibitory receptor recognizing the S100 protein family of DAMPs. This may help limit tissue damage induced by activated neutrophils.
AB - 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. In this study, we 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. Taken together, SIRL-1 is an inhibitory receptor recognizing the S100 protein family of DAMPs. This may help limit tissue damage induced by activated neutrophils.
KW - DAMP
KW - immune regulation
KW - inhibitory receptor
KW - S100
KW - SIRL-1
KW - Reactive Oxygen Species/metabolism
KW - Receptors, Immunologic/antagonists & inhibitors
KW - Neutrophil Activation/immunology
KW - Humans
KW - Alarmins/immunology
KW - Inflammation/immunology
KW - S100 Proteins/immunology
KW - Neutrophils/immunology
KW - Monocytes/immunology
KW - Signal Transduction/immunology
UR - http://www.scopus.com/inward/record.url?scp=85114002604&partnerID=8YFLogxK
U2 - 10.1002/eji.202149278
DO - 10.1002/eji.202149278
M3 - Article
C2 - 34145909
SN - 0014-2980
VL - 51
SP - 2210
EP - 2217
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 9
ER -