Fractalkine/CX3CR1: why a single chemokine-receptor duo bears a major and unique therapeutic potential.

IMPORTANCE OF THE FIELD: Fractalkine, also known as CX3CL1, is the unique member of the fourth class of chemokines and mediates both chemotaxis and adhesion of inflammatory cells via its highly selective receptor CX3CR1. Fractalkine mediates inflammatory responses and pain sensation and is involved in the pathogenesis and progression of numerous inflammatory disorders and malignancies. AREAS COVERED IN THIS REVIEW: We performed a Medline/PubMed search to detect all published studies that explored the role of fractalkine and CX3CR1 and the possibilities of therapeutic intervention in the fractalkine/CX3CR1 axis in a wide range of clinical disorders, using CX3CR1 blocking antibodies, different fractalkine antagonists, CX3CR1 depletion or transfection of fractalkine expression vectors. WHAT THE READER WILL GAIN: This review summarizes the role of fractalkine and its receptor CX3CR1 in various diseases, focusing on their high potential as novel therapeutic targets, with special emphasis on pancreatic diseases. TAKE HOME MESSAGE: The reviewed studies provide promising results demonstrating fractalkine and CX3CR1 as potential target molecules for future therapeutics that may attenuate pain, inflammation and furthermore serve as an anti-cancer therapy. However, to date, no therapeutics targeting fractalkine or CX3CR1 are in clinical use.