Plasmacytoid dendritic cells in multiple sclerosis: chemokine and chemokine receptor modulation by interferon-beta.
Plasmacytoid dendritic cells (pDCs) are present in peripheral blood, leptomeninges and demyelinating lesions in patients with multiple sclerosis (MS). The ability of pDCs to produce chemokines and express the chemokine receptor CCR7 in MS is not known. We studied pDCs in MS patients and healthy subjects. The ability of pDCs to up-regulate CCR7 was significantly increased in untreated MS patients as compared to healthy subjects. IFN-beta treatment significantly inhibited TLR9 agonist-specific secretion of chemokines, which are ligands for CCR5-positive Th1 cells (CCL3, CCL4, and CCL5), and impaired TLR9 agonist-induced up-regulation of CCR7 and IFN-alpha in MS patients. This finding represents a new immunomodulatory effect of IFN-beta in patients with multiple sclerosis.
Aung
Latt Latt
LL
Department of Neurology, UMDNJ-RWJMS, New Brunswick, NJ 08901, USA.
Fitzgerald-Bocarsly
Patricia
P
Dhib-Jalbut
Suhayl
S
Balashov
Konstantin
K
D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D018925:Chemokines / Q000378:metabolism*; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology* / Q000627:therapeutic use; D016898:Interferon-alpha / Q000378:metabolism; D016899:Interferon-beta / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000145:classification / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D019707:Receptors, Chemokine / Q000378:metabolism*; D055815:Young Adult
D018925:Chemokines; D007155:Immunologic Factors; D016898:Interferon-alpha; D019707:Receptors, Chemokine; D016899:Interferon-beta