TY - JOUR
T1 - CSF1R defines the mononuclear phagocyte system lineage in human blood in health and COVID-19
AU - Combes, Theo W.
AU - Orsenigo, Federica
AU - Stewart, Alexander
AU - Mendis, A. S.Jeewaka R.
AU - Dunn-Walters, Deborah
AU - Gordon, Siamon
AU - Martinez, Fernando O.
N1 - Publisher Copyright:
© 2021 The Author(s). Published by Oxford University Press on behalf of the British Society for Immunology.
PY - 2021/1/1
Y1 - 2021/1/1
N2 - 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 ex vivo 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.
AB - 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 ex vivo 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.
KW - COVID-19
KW - CSF1R
KW - blood
KW - dendritic cells
KW - human
KW - monocyte
UR - http://www.scopus.com/inward/record.url?scp=85117849849&partnerID=8YFLogxK
U2 - 10.1093/immadv/ltab003
DO - 10.1093/immadv/ltab003
M3 - 文章
AN - SCOPUS:85117849849
SN - 2732-4303
VL - 1
JO - Immunotherapy Advances
JF - Immunotherapy Advances
IS - 1
M1 - ltab003
ER -