title: The role of fractalkine (CX3CL1) in regulation of CD4(+) cell migration to the central nervous system in patients with relapsing-remitting multiple sclerosis.
abstract: Fractalkine (CX3CL1) levels are increased in the cerebrospinal fluid (CSF) of patients with clinically isolated syndrome (CIS), as well as in the CSF and serum samples from patients with relapsing-remitting multiple sclerosis (RRMS). A higher percentage of circulating CD4(+) T-cells expressed its surface receptor (CX3CR1) and intracellular adhesion molecule (ICAM-1) in RRMS patients in comparison to healthy controls (HCs). The CX3CR1(+)ICAM-1(+)CD4(+) T-cells are enriched in the CSF of the RRMS patients. In vitro migration studies revealed that CD4(+) T-cells, which migrated toward a CX3CL1 gradient, expressed higher levels of ICAM-1 than non-migrating cells. CX3CL1 significantly increased IFN-γ and TNF-α gene expression and IFN-γ secretion by CD4(+) T-cells derived from the RRMS patients. CX3CL1 upregulated ICAM-1 expression on the surface of RRMS patient-derived but not HC-derived CD4(+) T-cells. Thus, CX3CL1 induces recruitment of CX3CR1(+)ICAM-1(+)CD4(+) T-cells into the central nervous system (CNS) during the early inflammatory response in MS.
authors.affiliation: Department of Neurology, University of North Carolina at Chapel Hill, NC 27599, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Blauth
authors.affiliation: Department of Neurology, University of North Carolina at Chapel Hill, NC 27599, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Neurology, University of North Carolina at Chapel Hill, NC 27599, USA.
authors.forename: Manisha
authors.initials: M
authors.lastname: Chopra
authors.affiliation: Department of Neurology, University of North Carolina at Chapel Hill, NC 27599, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Rogan
authors.affiliation: Department of Neurology, University of North Carolina at Chapel Hill, NC 27599, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, NC 27599, USA. Electronic address: markovics@neurology.unc.edu.
authors.forename: Silva
authors.initials: S
authors.lastname: Markovic-Plese
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D000073883:CX3C Chemokine Receptor 1; D016022:Case-Control Studies; D002465:Cell Movement / Q000276:immunology*; D002490:Central Nervous System / Q000276:immunology* / Q000378:metabolism; D054428:Chemokine CX3CL1 / Q000134:cerebrospinal fluid / Q000276:immunology*; D003711:Demyelinating Diseases / Q000134:cerebrospinal fluid / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000134:cerebrospinal fluid / Q000378:metabolism*; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000134:cerebrospinal fluid / Q000276:immunology* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D019707:Receptors, Chemokine / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D000073883:CX3C Chemokine Receptor 1; C515538:CX3CL1 protein, human; C095235:CX3CR1 protein, human; D054428:Chemokine CX3CL1; C573420:ICAM1 protein, human; D012333:RNA, Messenger; D019707:Receptors, Chemokine; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma
keywords: CX3CL1;; CX3CR1;; ICAM-1;; IFN-γ;; Multiple sclerosis; TNF-α;