Combes Theo W, Orsenigo Federica, Stewart Alexander, Mendis A S Jeewaka R, Dunn-Walters Deborah, Gordon Siamon, Martinez Fernando O
Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK.
Department of Biotechnology and Biosciences, Università degli Studi di Milano-Bicocca, Milan, Italy.
Immunother Adv. 2021 Feb 17;1(1):ltab003. doi: 10.1093/immadv/ltab003. eCollection 2021 Jan.
Mononuclear phagocytes defend tissues, present antigens, and mediate recovery and healing. To date, we lack a marker to unify mononuclear phagocytes in humans or that informs us about their origin. Here, we reassess mononuclear phagocyte ontogeny in human blood through the lineage receptor CSF1R, in the steady state and in COVID-19. We define CSF1R as the first sensitive and reproducible pan-phagocyte lineage marker, to identify and enumerate all conventional monocytes, and the myeloid dendritic cells. In the steady state, CSF1R is sufficient for sorting and immuno-magnetic isolation. In pathology, changes in CSF1R are more sensitive than CD14 and CD16. In COVID-19, a significant drop in membrane CSF1R is useful for stratifying patients, beyond the power of cell categories published thus far, which fail to capture COVID-19 specific events. Importantly, CSF1R defines cells which are neither conventional monocytes nor DCs, which are missed in published analysis. CSF1R decrease can be linked to high CSF1 levels. Blood assessment of CSF1R+ cells opens a developmental window to the Mononuclear Phagocyte System in transit from bone marrow to tissues, supports isolation and phenotypic characterisation, identifies novel cell types, and singles out CSF1R inhibition as therapeutic target in COVID-19 and other diseases.
单核吞噬细胞可保护组织、呈递抗原并介导恢复与愈合。迄今为止，我们缺乏一种能够统一人类单核吞噬细胞或告知其起源的标志物。在此，我们通过谱系受体集落刺激因子1受体（CSF1R），在稳态和新冠肺炎（COVID-19）状态下重新评估人类血液中的单核吞噬细胞个体发生。我们将CSF1R定义为首个敏感且可重复的全吞噬细胞谱系标志物，用于识别和计数所有常规单核细胞以及髓样树突状细胞。在稳态下，CSF1R足以用于细胞分选和免疫磁珠分离。在病理学中，CSF1R的变化比CD14和CD16更为敏感。在COVID-19中，膜CSF1R的显著下降有助于对患者进行分层，其作用超过了迄今为止公布的细胞分类能力，因为这些分类未能捕捉到COVID-19的特异性事件。重要的是，CSF1R可定义既非常规单核细胞也非树突状细胞的细胞，而这些细胞在已发表的分析中被遗漏。CSF1R的减少可能与CSF1水平升高有关。对CSF1R+细胞进行血液评估为从骨髓到组织过渡中的单核吞噬细胞系统打开了一个发育窗口，支持细胞分离和表型特征分析，识别新型细胞类型，并将CSF1R抑制确定为COVID-19和其他疾病的治疗靶点。
