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Fractalkine (CX3CL1) and Its Chemoattractant and Adhesion Molecule Properties in Health and Disease, 2nd Edition

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Department of Biophysics, Physiology and Pathophysiology, Faculty of Health Sciences, Medical University of Warsaw, Chalubinskiego 5 (4th Floor), 02-004 Warsaw, Poland
Interests: inflammation; cytokine network; sirtuins; endothelial signaling; human placenta; stem cells; pathophysiology of diabetes

Special Issue Information

Dear Colleagues,

Fractalkine (FKN), also known as CX3CL1, is the only member of the chemokine family containing a three-amino-acid motif between the two cysteines (C-X-X-X-C) and a mucin-like domain. This chemokine is made up of 373 amino acids and is synthesized as a transmembrane molecule. Moreover, after cleavage by the TNFα-converting enzyme ADAM17, FKN can exist in a soluble form. These peculiar structural characteristics of fractalkine go hand-in-hand with its unique functional properties, as FKN combines the features of a chemoattractant and an adhesion molecule. Both of these functions require the presence of a specific and sole FKN receptor, CX3C motif chemokine receptor 1 (CX3CR1), also known as G-protein coupled receptor 13 (GPR13). Considering that CX3CR1 expression has been demonstrated on many different cells, including but not limited to monocytes, microglia and macrophages, dendritic cells, T cells, natural killer (NK) cells, vascular endothelial cells, smooth and skeletal muscle cells, neurons, hepatocytes, adipocytes and endometrial cells, FKN signaling may be crucial in health and disease. FKN-CX3CR1 signaling exerts distinct functions in different tissue compartments and may be involved in a wide spectrum of biological phenomena, such as cell adhesion and chemotaxis, immune response, inflammation, apoptosis, implantation, angiogenesis, atherosclerosis, formation of endometriotic foci, neurotoxicity or carcinogenesis.

This Special Issue is dedicated to all aspects of FKN signaling, including both physiological and pathologic conditions. It may be extremely interesting to present the reasons for recognizing the FKN-CX3CR1 signaling pathway as the main therapeutic target in a given disease.

When considering your submission, please keep in mind that IJMS is a journal of molecular science. However, submissions of clinical studies that include biomolecular experiments or pathological research with case sample data are welcomed.

Prof. Dr. Dariusz Szukiewicz
Guest Editor

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Keywords

  • fractalkine
  • transmembrane fractalkine
  • soluble fractalkine
  • fractalkine receptor
  • CX3CL1-CX3CR1 signaling
  • inflammation
  • chemokine
  • cell adhesion
  • chemotaxis
  • immune response
  • angiogenesis
  • implantation
  • atherosclerosis
  • carcinogenesis

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Published Papers (1 paper)

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Review

31 pages, 3144 KB  
Review
Fractalkine (Chemokine CX3CL1) Signaling During Placentation and Placental Function
by Dariusz Szukiewicz
Int. J. Mol. Sci. 2026, 27(3), 1172; https://doi.org/10.3390/ijms27031172 - 23 Jan 2026
Viewed by 585
Abstract
Precise postimplantation regulation of placental development with trophoblast invasion of uterine spiral arteries and the generation of low-resistance circulation within the utero-fetal unit are crucial for the further development of pregnancy. Cytokines, including chemokines, are crucial for ensuring placental function throughout pregnancy. The [...] Read more.
Precise postimplantation regulation of placental development with trophoblast invasion of uterine spiral arteries and the generation of low-resistance circulation within the utero-fetal unit are crucial for the further development of pregnancy. Cytokines, including chemokines, are crucial for ensuring placental function throughout pregnancy. The CX3CL1 chemokine (fractalkine), occurring in its membrane-bound form and as a soluble chemokine (sCX3CL1), acts on its sole receptor, namely, CX3CR1, creating a signaling axis that orchestrates the balance of cellular interactions, immune responses, and tissue remodeling needed at every stage of a healthy pregnancy. CX3CL1/CX3CR1 signaling is characterized by the activation of several downstream signaling cascades that interact with numerous pathways, coordinate with other receptors and modulate the expression of relevant genes. This review presents the current state of knowledge regarding the role of CX3CL1 and its interaction with CX3CR1 in establishing placental homeostasis during placentation, and it discusses the contribution of disturbances in this interaction to placental dysfunction. These disturbances are part of the pathomechanisms of specific pregnancy complications, including preeclampsia (PE) and diabetes. The potential to target the CX3CL1/CX3CR1 axis via therapeutic intervention at the level of the placenta in PE- and diabetes-complicated pregnancy is the subject of ongoing research. Full article
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