Frequency of blood CX3CR1-positive natural killer cells correlates with disease activity in multiple sclerosis patients.
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) characterized by enormous variability in its clinical presentation and course, and for which clear diagnostic parameters are lacking. Here we performed an RNA screen in peripheral mononuclear cells from relapsing-remitting (RR) and primary progressive (PP) MS patients compared with healthy donors (HD) that indicated, among other findings, a role for the chemokine receptor CX3CR1 as a diagnostic marker. Gene expression and flow cytometric analyses demonstrated a significantly lower expression of CX3CR1 in MS patients compared with healthy individuals. The subpopulation of cells responsible for causing this reduced expression of CX3CR1 consisted exclusively of natural killer (NK) cells. Importantly, we found a correlation between disease activity and frequency of CX3CR1-positive NK cells in RRMS patients. These findings emphasize the role of NK cells in the development and course of MS and provide evidence for CX3CR1 expression as a marker for MS patients and disease activity.
Infante-Duarte
Carmen
C
Institute of Neuroimmunology, Charité University Hospital Berlin, Germany.
Weber
Alexandra
A
Krätzschmar
Jörn
J
Prozorovski
Timour
T
Pikol
Susan
S
Hamann
Isabell
I
Bellmann-Strobl
Judith
J
Aktas
Orhan
O
Dörr
Jan
J
Wuerfel
Jens
J
Stürzebecher
Claus-Steffen
CS
Zipp
Frauke
F
D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000737:chemistry; D019921:Biotinylation; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D000073883:CX3C Chemokine Receptor 1; D002470:Cell Survival; D015536:Down-Regulation; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation; D007694:Killer Cells, Natural / Q000166:cytology*; D008297:Male; D008565:Membrane Proteins / Q000097:blood*; D008875:Middle Aged; D008954:Models, Biological; D009103:Multiple Sclerosis / Q000097:blood* / Q000175:diagnosis; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood; D020411:Oligonucleotide Array Sequence Analysis; D012313:RNA / Q000737:chemistry; D019707:Receptors, Chemokine / Q000097:blood*; D012008:Recurrence; D012074:Remission Induction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D015854:Up-Regulation
D000911:Antibodies, Monoclonal; D000073883:CX3C Chemokine Receptor 1; C095235:CX3CR1 protein, human; D008565:Membrane Proteins; D019707:Receptors, Chemokine; D012313:RNA