Fractalkine, a CX3C chemokine, is expressed by dendritic cells and is up-regulated upon dendritic cell maturation

Abstract

The lone CX3C chemokine, fractalkine (FK), is expressed in a membrane‐bound form on activated endothelial cells and mediates attachment and firm adhesion of T cells, monocytes and NK cells. We now show that FK is associated with dendritic cells (DC) in epidermis and lymphoid organs. In normal human skin, dual‐color fluorescence microscopy co‐localized FK expression with Langerhans cells expressing CD1a. In tonsil, FK‐positive DC expressed CD83, a marker for mature DC. Human and murine cultured DC up‐regulated FK mRNA expression with maturation. Furthermore, CD40 ligation, but not TNF‐α or lipopolysaccharide treatment, of activated, migratory DC that had migrated from skin explants resulted in a 2.5‐fold increase of surface expression of FK without significant alterations of expression of CD80, CD86, CD54 or MHC class II. Since FK mediates adhesion of T cells to activated endothelial cells, the increased expression of FK during DC maturation (and particularly by CD40 ligation) may play a role in the ability of T cells and mature DC to form conjugates and engage in cell‐cell communication.

High Cytotoxic and Specific Migratory Potencies of Senescent CD8+CD57+ Cells in HIV-Infected and Uninfected Individuals

“…In the mouse model, FKN is expressed by DC in lymph node T cell areas (50). In human and murine models, CX3CL1 can be expressed by DC in epidermis and secondary lymphoid organs (51). These observations add new insight into the potential interaction of CD8 ϩ CD57 ϩ CX3CR1 ϩ with different population of DC in tissues and lymphoid organs.…”

Soluble Fractalkine Prevents Monocyte Chemoattractant Protein-1-Induced Monocyte Migration via Inhibition of Stress-Activated Protein Kinase 2/p38 and Matrix Metalloproteinase Activities

“…FKN, the unique member of the CX 3 C family, is markedly induced at the surface of endothelial cells in response to IL-1 and TNF-␣ (18). In its membrane form, FKN behaves essentially as an adhesion molecule that interacts with its coligand CX 3 CR1 expressed at the surface of T lymphocytes, NK cells, monocytes (18,22), dendritic cells (23,24), microglial cells (63), and neurons (27). The G-coupled CX 3 CR1 also transduces, in addition to the intrinsic adhesive function of FKN, signals that augment the integrin avidity for their ligands (64).…”

“…Thus, FKN represents a new class of chemokine that behaves as a true chemokine in its soluble form, whereas it acts as an adhesion molecule in its membrane form (18). FKN binds specifically to the unique CX 3 CR1 receptor that, in the immune system, has been shown to be expressed on the majority of NK cells, monocytes, some T cell subpopulations (18,22), and dendritic cells (23,24). Curiously, s-FKN, which behaves as a potent chemottractant for NK cells, T cells, and dendritic cells, exerts poor or no effect on monocyte migration, albeit this lineage expresses the CX 3 CR1 receptor (19,25).…”

Differential expression of the fractalkine chemokine receptor (CX3CR1) in human monocytes during differentiation

“…39,58 In contrast, it has been reported that DCs express the corresponding ligand, chemokine CX 3 CL1, which was increased during DC maturation (particularly by CD40 ligation). 20 Stable CX 3 CR1 expression during the DC maturation process would contradict the maturation state that is dependent on the expression of other CC-chemokine receptors, which may ensure the directional traffic of immature DCs from blood to target sites. 59 The controversial conclusion about CX 3 CR1 protein expression in DCs could be derived from the presence of CX 3 CR1 mRNA, which was also observed under our experimental conditions, or the use of DCs from different origins or obtained through different purification protocols.…”

“…15,16 The full-length molecule can be cleaved from the cell membrane by tumor necrosis factor-a-converting enzyme, a member of the ADAM (disintegrin and metalloprotease) family, and ADAM10, to produce a soluble form that includes the chemokine domain and most of the stalk region. 15 CX 3 CL1 is expressed on the surface of endothelial cells, 17 epithelial cells, 17,18 DCs 19,20 and neurons 21 and is induced by pro-inflammatory cytokines, such as interleukin (IL)-1 and tumor necrosis factor-a. 22,23 The CX 3 CL1 receptor, CX 3 CR1, is capable of mediating both leukocyte migration and firm adhesion.…”