REVIEW article

Front. Immunol.

Sec. Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders

Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1576371

Beyond Inflammation: The Multifaceted Therapeutic Potential of Targeting the CXCL8-CXCR1/2 Axis in Type 1 Diabetes

Provisionally accepted
Georgia FousteriGeorgia Fousteri1Meghan JonesMeghan Jones2Rubina NovelliRubina Novelli1Serena BoccellaSerena Boccella1Laura BrandoliniLaura Brandolini1Andrea AraminiAndrea Aramini1Paolo PozzilliPaolo Pozzilli3Marcello AllegrettiMarcello Allegretti1*
  • 1Dompé farmaceutici S.p.A., Milano, Italy
  • 2Dompé US, San Mateo, United States
  • 3Campus Bio-Medico University, Rome, Lazio, Italy

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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.

Keywords: type 1 diabetes, Inflammation, Chemokines, Neutrophils, CXCL8, Interleukin-8, CXCR1, CXCR2

Received: 13 Feb 2025; Accepted: 25 Jun 2025.

Copyright: © 2025 Fousteri, Jones, Novelli, Boccella, Brandolini, Aramini, Pozzilli and Allegretti. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Marcello Allegretti, Dompé farmaceutici S.p.A., Milano, 20122, Italy

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Supplementary Material