Pathophysiological Roles of the CX3CL1-CX3CR1 Axis in Renal Disease, Cardiovascular Disease, and Cancer
Yuya Iwahashi, Yuko Ishida, Naofumi Mukaida, Toshikazu Kondo
Abstract
CX3CL1 and its unique receptor, CX3CR1, are leukocyte migration factors and are involved in the pathogenesis and progression of many inflammatory diseases and malignancies. The CX3CL1-CX3CR1 axis induces a variety of responses, including cell proliferation, migration, invasion, and apoptosis resistance. CX3CL1 is a transmembrane protein, and proteolysis generates a soluble form. The membrane and soluble forms of CX3CL1 exhibit different functions, but both bind to the chemokine receptor CX3CR1. The CX3CL1-CX3CR1 axis is a chemokine system that has attracted attention not only as a therapeutic target but also as a potentially useful diagnostic and prognostic marker for disease. Many studies have reported that the CX3CL1-CX3CR1 axis is involved in disease progression, but more recently there are scattered reports suggesting that it is involved in disease suppression. In this article, we summarize the latest findings on the pathophysiological role of the CX3CL1-CX3CR1 axis, with a particular focus on renal disease, cardiovascular disease, and cancer.