Role of the CX3CL1-CX3CR1 axis in renal disease

Abstract

Excessive infiltration of immune cells into the kidney is a key feature of acute and chronic kidney diseases. The family of chemokines comprises key drivers of this process. Fractalkine [chemokine (C-X3-C motif) ligand 1 (CX₃CL1)] is one of two unique chemokines synthesized as a transmembrane protein that undergoes proteolytic cleavage to generate a soluble species. Through interacting with its cognate receptor, chemokine (C-X3-C motif) receptor 1 (CX₃CR1), CX₃CL1 was originally shown to act as a conventional chemoattractant in the soluble form and as an adhesion molecule in the transmembrane form. Since then, other functions of CX₃CL1 beyond leukocyte recruitment have been described, including cell survival, immunosurveillance, and cell-mediated cytotoxicity. This review summarizes diverse roles of CX₃CL1 in kidney disease and potential uses as a therapeutic target and novel biomarker. As the CX₃CL1-CX₃CR1 axis has been shown to contribute to both detrimental and protective effects in various kidney diseases, a thorough understanding of how the expression and function of CX₃CL1 are regulated is needed to unlock its therapeutic potential.

Keywords: chemokine (C-X3-C motif) receptor 1; chemokines; fractalkine; inflammation; kidney disease.