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The role of fractalkine (CX3CL1) in regulation of CD4+ cell migration to the central nervous system in patients with relapsing–remitting multiple sclerosis
Kevin Blauth, Xin Zhang, Manisha Chopra, Sarah Rogana, Silva Markovic-Plesea
Clinical Immunology, In Press, Uncorrected Proof, Available online 14 January 2015
Fractalikine (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 expressions 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.