AUTHOR=Fousteri Georgia , Jones Meghan , Novelli Rubina , Boccella Serena , Brandolini Laura , Aramini Andrea , Pozzilli Paolo , Allegretti Marcello 

TITLE=Beyond inflammation: the multifaceted therapeutic potential of targeting the CXCL8-CXCR1/2 axis in type 1 diabetes

JOURNAL=Frontiers in Immunology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1576371

DOI=10.3389/fimmu.2025.1576371

ISSN=1664-3224

ABSTRACT=Identifying novel therapeutic targets involved in the multiple mechanisms underlying the complex pathophysiology of type 1 diabetes (T1D) could change the natural history of this disease. The CXCL8-CXCR1/2 axis is emerging as a therapeutic target with a crucial, multifaceted role in T1D pathophysiology. CXCL8-dependent neutrophil chemotaxis to the pancreas precedes autoimmunity, and CXCR1/2 blockade mitigates insulitis and T1D development in preclinical models. In parallel, CXCL8 can act in a β cell-autonomous manner, and exert non-immune actions on adipocytes, hepatocytes, podocytes, and muscle cells that contribute to insulin resistance and diabetic complications. In this review, we delineate compelling evidence of immune and non-immune actions of the axis in the onset and progression of T1D. We show that the CXCL8-CXCR1/2 axis represents a promising therapeutic target for the prevention/reversal of T1D, with a meaningful potential clinical advantage conveyed by its role in multiple components of the pathology and diabetic complications.