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

Georgia Fousteri1, Meghan Jones2, Rubina Novelli1

  • 1Research & Development, Dompé Farmaceutici S.p.A, Milan, Italy.

Frontiers in Immunology
|July 28, 2025
PubMed

Insights

The CXCL8-CXCR1/2 axis plays a key role in type 1 diabetes (T1D) by promoting inflammation and insulin resistance. Blocking this axis shows promise for preventing and reversing T1D and its complications.

Area of Science:

  • Immunology
  • Endocrinology
  • Molecular Biology

Background:

  • Type 1 diabetes (T1D) involves complex pathophysiology requiring novel therapeutic targets.
  • The CXCL8-CXCR1/2 axis is increasingly recognized for its significant role in T1D.

Purpose of the Study:

  • To review the immune and non-immune actions of the CXCL8-CXCR1/2 axis in T1D onset and progression.
  • To highlight the therapeutic potential of targeting this axis for T1D management.

Main Methods:

  • Review of preclinical models and existing literature on the CXCL8-CXCR1/2 axis in T1D.
  • Analysis of immune cell migration (neutrophil chemotaxis) and non-immune cell effects.

Main Results:

  • CXCL8-dependent neutrophil infiltration precedes T1D autoimmunity.
  • CXCR1/2 blockade reduces insulitis and T1D development in models.
  • CXCL8 also impacts non-immune cells, contributing to insulin resistance and complications.

Conclusions:

  • The CXCL8-CXCR1/2 axis is a critical factor in T1D pathogenesis.
  • Targeting this axis offers a promising strategy for T1D prevention and reversal.
  • Its multifaceted role presents a significant clinical advantage for treating T1D and its complications.
Keywords:
CXCL8CXCR1CXCR2chemokinesinflammationinterleukin-8neutrophilstype 1 diabetes

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