CC chemokine receptor 8 in the central nervous system is associated with phagocytic macrophages.
CC chemokine receptor 8 (CCR8) has been detected in vitro on type 2 helper and regulatory lymphocytes, which might exert beneficial functions in multiple sclerosis (MS) and on macrophages and microglia, possibly promoting tissue injury in MS lesions. To discriminate the relevant expression pattern in vivo, we defined the cell types that expressed CCR8 in MS lesions and determined the relationship of CCR8 expression and demyelinating activity. CCR8 was not expressed on T cells but was associated with phagocytic macrophages and activated microglia in MS lesions and directly correlated with demyelinating activity. To identify factors associated with CCR8 expression, the study was extended to other central nervous system (CNS) pathologies. CCR8 was consistently expressed on phagocytic macrophages and activated microglia in stroke and progressive multifocal leukoencephalopathy, but not expressed on microglia in pathologies that lacked phagocytic macrophages such as senile change of the Alzheimer's type. CCR8 was up-regulated by macrophage differentiation and activating stimuli in vitro. In summary CNS CCR8 expression was associated with phagocytic macrophages and activated microglial cells in human CNS diseases, suggesting that CCR8 may be a feasible target for therapeutic intervention in MS. CCR8 expression may also indicate a selective program of mononuclear phagocyte gene expression.
Trebst
Corinna
C
Department of Neurosciences, The Lerner Research Institute, Cleveland, Ohio 44195, USA.
Staugaitis
Susan M
SM
Kivisäkk
Pia
P
Mahad
Don
D
Cathcart
Martha K
MK
Tucky
Barbara
B
Wei
Tao
T
Rani
Mysore R Sandhya
MR
Horuk
Richard
R
Aldape
Kenneth D
KD
Pardo
Carlos A
CA
Lucchinetti
Claudia F
CF
Lassmann
Hans
H
Ransohoff
Richard M
RM
D000328:Adult; D001344:Autopsy; D001706:Biopsy; D002493:Central Nervous System Diseases / Q000276:immunology* / Q000473:pathology*; D019742:Chemokines, CC / Q000032:analysis; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000276:immunology*; D008297:Male; D017628:Microglia / Q000276:immunology*; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology* / Q000473:pathology*; D010587:Phagocytosis; D054401:Receptors, CCR8; D019707:Receptors, Chemokine / Q000032:analysis* / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018418:Th2 Cells / Q000276:immunology
C103330:CCR8 protein, human; D019742:Chemokines, CC; D054401:Receptors, CCR8; D019707:Receptors, Chemokine