TY - JOUR
T1 - Peripherally derived macrophages can engraft the brain independent of irradiation and maintain an identity distinct from microglia
AU - Cronk, James C.
AU - Filiano, Anthony J.
AU - Louveau, Antoine
AU - Marin, Ioana
AU - Marsh, Rachel
AU - Ji, Emily
AU - Goldman, Dylan H.
AU - Smirnov, Igor
AU - Geraci, Nicholas
AU - Acton, Scott
AU - Overall, Christopher C.
AU - Kipnis, Jonathan
N1 - Publisher Copyright:
© 2018 Cronk et al.
PY - 2018/6/1
Y1 - 2018/6/1
N2 - Peripherally derived macrophages infiltrate the brain after bone marrow transplantation and during central nervous system (CNS) inflammation. It was initially suggested that these engrafting cells were newly derived microglia and that irradiation was essential for engraftment to occur. However, it remains unclear whether brain-engrafting macrophages (beMϕs) acquire a unique phenotype in the brain, whether long-term engraftment may occur without irradiation, and whether brain function is affected by the engrafted cells. In this study, we demonstrate that chronic, partial microglia depletion is sufficient for beMϕs to populate the niche and that the presence of beMϕs does not alter behavior. Furthermore, beMϕs maintain a unique functional and transcriptional identity as compared with microglia. Overall, this study establishes beMϕs as a unique CNS cell type and demonstrates that therapeutic engraftment of beMϕs may be possible with irradiation-free conditioning regimens.
AB - Peripherally derived macrophages infiltrate the brain after bone marrow transplantation and during central nervous system (CNS) inflammation. It was initially suggested that these engrafting cells were newly derived microglia and that irradiation was essential for engraftment to occur. However, it remains unclear whether brain-engrafting macrophages (beMϕs) acquire a unique phenotype in the brain, whether long-term engraftment may occur without irradiation, and whether brain function is affected by the engrafted cells. In this study, we demonstrate that chronic, partial microglia depletion is sufficient for beMϕs to populate the niche and that the presence of beMϕs does not alter behavior. Furthermore, beMϕs maintain a unique functional and transcriptional identity as compared with microglia. Overall, this study establishes beMϕs as a unique CNS cell type and demonstrates that therapeutic engraftment of beMϕs may be possible with irradiation-free conditioning regimens.
UR - http://www.scopus.com/inward/record.url?scp=85048117956&partnerID=8YFLogxK
U2 - 10.1084/jem.20180247
DO - 10.1084/jem.20180247
M3 - Article
C2 - 29643186
AN - SCOPUS:85048117956
SN - 0022-1007
VL - 215
SP - 1627
EP - 1647
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 6
ER -