Center for Translational Immunology, Dept. Immunology, University Medical Center Utrecht, Utrecht University, Oncode Institute, Utrecht, The Netherlands.
Theoretical Biology and Bioinformatics, Department of Biology, Utrecht University, Utrecht, The Netherlands.
J Leukoc Biol. 2022 Feb;111(2):367-377. doi: 10.1002/JLB.2A0520-334R. Epub 2021 Apr 22.
Inhibitory 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.
抑制性和激活性免疫受体在调节感染过程中免疫反应的幅度和持续时间以及在维持稳态条件下的免疫平衡方面发挥着关键作用。人类的 CD200 受体 (CD200R) 基因家族编码一个抑制性受体 CD200R1 和一个假定的激活成员 CD200R1 样 (CD200R1L)。研究表明，CD200R1L 在内生性地表达于人类中性粒细胞，并通过 Syk、PI3Kβ、PI3Kδ 和 Rac GTPase 信号通路激活细胞功能，如活性氧 (ROS) 的产生。系统发生分析表明，CD200R1L 存在于从鸟类到灵长类等脊椎动物的许多物种中，这表明该受体的进化保守对于对抗共同进化的病原体至关重要。产生 CD200R1L 的 CD200R 基因的重复事件在进化过程中发生了多次，支持了 CD200R1L 的趋同进化。在我们的系统发生树中，在大多数物种中，CD200R1L 的分支长度比 CD200R1 长，这表明 CD200R1L 的进化速度比 CD200R1 快。据推测，CD200R1L 代表人类中性粒细胞上一个迄今为止尚未表征的激活受体。
