CD200R1L is a functional evolutionary conserved activating receptor in human neutrophils

• DOI: 10.1002/jlb.2a0520-334r
• Publication Date: 2021-04-22T14:58:53Z
• Authors: M Inês Pascoal Ramos; Can Keşmir; Jorn E Stok; Ruben Geerdink; Nikolaos Satravelas; Geertje H A Weste...; Linde Meyaard; Michiel van der V...
• Keywords: reactive oxygen species; 0301 basic medicine; Neutrophils; Immunology; Interleukin-8; NETosis; Antibodies, Monoclonal; Cell Biology; phylogeny; rac GTP-Binding Proteins; 3. Good health; Evolution, Molecular; Phosphatidylinositol 3-Kinases; 03 medical and health sciences; Receptors, Signal Transduction and Genes; Orexin Receptors; Immunology and Allergy; Humans; Syk Kinase; Reactive Oxygen Species; Phylogeny

AbstractInhibitory and activating immune receptors play a key role in modulating the amplitude and duration of immune responses during infection and in maintaining immune balance in homeostatic conditions. The CD200 Receptor (CD200R) gene family in humans encodes one inhibitory receptor, CD200R1, and one putative activating member, CD200R1 Like (CD200R1L). It is demonstrated that CD200R1L is endogenously expressed by human neutrophils and activates cellular functions such as reactive oxygen species (ROS) production via Syk, PI3Kβ, PI3Kδ, and Rac GTPase signaling. Phylogenetic analysis shows that CD200R1L is present in many species among vertebrates, ranging from birds to primates, suggesting that evolutionary conservation of this receptor is critical for protection against co-evolving pathogens. The duplication event that generated CD200R1L from CD200R occurred several times throughout evolution, supporting convergent evolution of CD200R1L. In our phylogenetic trees, CD200R1L has longer branch lengths than CD200R1 in most species, suggesting that CD200R1L is evolving faster than CD200R1. It is proposed that CD200R1L represents a hitherto uncharacterized activating receptor on human neutrophils.