Work

The differences of clinical features and neutrophils’ stress between IL-17 positive and negative patients of type 1 diabetes mellitus

Year: 2025

Type: article

Abstract: BACKGROUND: Type 1 diabetes mellitus (T1D) is an autoimmune disorder characterized by immune-mediated destruction of pancreatic β-cells, resulting in lifelong insulin dependence. Interleukin-17A (IL-17A), associated with T1D progression and complications, can mobilize and activate neutrophils to release lytic enzymes, reactive oxygen species, and cytokines, thereby promoting systemic inflammation and cell destruction; such neutrophil-driven responses have also been implicated in autoimmune diseases, including diabetes. This study aimed to compare the clinical characteristics and neutrophil stress of IL-17A-positive and -negative T1D patients. METHODS: 37 patients were enrolled between May 2023 and April 2024 at Department of Pediatric Endocrinology, Changhua Christian Children's Hospital. In addition to clinical characteristics, peripheral blood neutrophils were isolated to analyze antioxidant-related protein, autophagy, and respiratory bursts. Serum cytokine profiles were also assessed. RESULTS: 27 patients were IL-17A-positive. At disease onset, they were younger and had lower absolute neutrophil counts. Years later, they showed higher LDL, with HDL declining over time and TG trending upward. All participants were Vitamin D insufficiency, and IL-17A levels correlated positively with vitamin D levels. Neutrophils in the peripheral blood displayed reduced xCT, GPX4, and HO-1, increased LC3II/LC3I ratios with decreased p62, and greater ROS production upon stimulation. Serum IL-5 levels were significantly higher, with eotaxin trending higher. CONCLUSION: IL-17A-positive T1D is associated with earlier onset. As the disease progresses, it leads to an increased risk of dyslipidemia and the development of type 2 inflammation. Furthermore, the neutrophils in these patients suggestive of ferroptosis, defining a distinct phenotype for potential targeted therapy.

Source: Journal of Microbiology Immunology and Infection

DOI: 10.1016/j.jmii.2025.11.005