Developmental plasticity of CNS microglia.
Microglia arise from CD45(+) bone marrow precursors that colonize the fetal brain and play a key role in central nervous system inflammatory conditions. We report that parenchymal microglia are uncommitted myeloid progenitors of immature dendritic cells and macrophages by several criteria, including surface expression of "empty" class II MHC protein and their cysteine protease (cathepsin) profile. Microglia express receptors for stem cell factor and can be skewed toward more dendritic cell or macrophage-like profiles in response to the lineage growth factors granulocyte/macrophage colony-stimulating factor or macrophage colony-stimulating factor. Thus, in contrast to other organs, where terminally differentiated populations of resident dendritic cells and/or macrophages outnumber colonizing precursors, the majority of microglia within the brain remain in an undifferentiated state.
Santambrogio
L
L
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA 02115, USA. laura_santambrogio@dfci.harvard.edu
Belyanskaya
S L
SL
Fischer
F R
FR
Cipriani
B
B
Brosnan
C F
CF
Ricciardi-Castagnoli
P
P
Stern
L J
LJ
Strominger
J L
JL
Riese
R
R
D000818:Animals; D002403:Cathepsins / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology; D008565:Membrane Proteins / Q000096:biosynthesis; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D009473:Neuronal Plasticity / Q000276:immunology*; D019089:Stem Cell Factor / Q000096:biosynthesis
D000949:Histocompatibility Antigens Class II; D008565:Membrane Proteins; D019089:Stem Cell Factor; C084881:flt3 ligand protein; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D002403:Cathepsins