The CXCR1/2 Pathway: Involvement in Diabetes Pathophysiology and Potential Target for T1D Interventions.
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.
San Raffaele Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy, citro.antonio@hsr.it.
Antonio
A
Citro
Elisa
E
Cantarelli
Lorenzo
L
Piemonti
D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000503:physiopathology* / Q000628:therapy; D006801:Humans; D007515:Islets of Langerhans / Q000276:immunology / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology; D023062:Receptors, Interleukin-8A / Q000276:immunology / Q000378:metabolism; D023063:Receptors, Interleukin-8B / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction
D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B