The CXCR1/2 Pathway: Involvement in Diabetes Pathophysiology and Potential Target for T1D Interventions

Abstract

Although numerous chemokine/chemokine receptor pathways have been described to be implicated in the pathogenesis of type 1 diabetes (T1D), the CXCR1/2 axis has recently been proved to be crucial for leucocyte recruitment involved in insulitis and β cell damage. Multiple strategies blocking the CXCR1/2 pathway are available such as neutralizing antibodies, small molecules and peptide-derived inhibitors. They were firstly and widely used in cancer thanks to their anti-tumorigenic activity and only recently they were tested as a new interventional approach for T1D. As well, CXCR1/2 inhibition has been demonstrated to prevent inflammation- and autoimmunity-mediated damage of the pancreatic islets through inhibiting the migration of CXCR1/2-expressing cells. Among them, neutrophils, macrophages, and, although to a smaller extent, lymphoid cells are the main CXCR1/2-expressing cells. These results supported the active role of the innate immunity in the autoimmune process and opened new interventional approaches for the management of T1D.