ROS-producing immature neutrophils in giant cell arteritis are linked to vascular pathologies
Lihui Wang1, Zhichao Ai1, Tariq Khoyratty1
1Kennedy Institute of Rheumatology and.
Insights
Immature neutrophils are key to giant cell arteritis (GCA) and other systemic vasculitides. These cells drive disease by resisting apoptosis and damaging blood vessels, offering new therapeutic targets.
Area of Science:
- Immunology
- Cell Biology
- Pathology
Background:
- Giant cell arteritis (GCA) is a prevalent systemic vasculitis in adults.
- Current diagnostic and prognostic tools for GCA lack reliability.
Purpose of the Study:
- To identify specific immune cell populations associated with GCA.
- To elucidate the role of these cells in disease pathogenesis and treatment response.
Main Methods:
- Single-cell technologies were employed to analyze immune cells in GCA patients' blood.
- In vitro coculture systems were used to study neutrophil function.
Main Results:
- Specific immature neutrophil populations (CD66b+CD15+CD10lo/-CD64- band neutrophils and CD66bhiCD15+CD10lo/-CD64+/bright myelocytes/metamyelocytes) were identified and linked to GCA phenotype and treatment response.
- These immature neutrophils exhibited resistance to apoptosis, prolonged vascular presence, platelet interaction, and extravasation into temporal artery tissues.
- In vitro studies demonstrated that these neutrophils generate reactive oxygen species, increasing protein oxidation and endothelial permeability.
- Similar neutrophil populations were observed in other systemic vasculitides.
Conclusions:
- Immature neutrophils play a critical role in the pathogenesis of GCA and potentially other systemic vasculitides.
- These findings establish a cellular signature for GCA.
- The study suggests novel therapeutic strategies targeting immature neutrophils in systemic vascular inflammation.
Abstract:
Giant cell arteritis (GCA) is a common form of primary systemic vasculitis in adults, with no reliable indicators of prognosis or treatment responses. We used single cell technologies to comprehensively map immune cell populations in the blood of patients with GCA and identified the CD66b+CD15+CD10lo/-CD64- band neutrophils and CD66bhiCD15+CD10lo/-CD64+/bright myelocytes/metamyelocytes to be unequivocally associated with both the clinical phenotype and response to treatment. Immature neutrophils were resistant to apoptosis, remained in the vasculature for a prolonged period of time, interacted with platelets, and extravasated into the tissue surrounding the temporal arteries of patients with GCA. We discovered that immature neutrophils generated high levels of extracellular reactive oxygen species, leading to enhanced protein oxidation and permeability of endothelial barrier in an in vitro coculture system. The same populations were also detected in other systemic vasculitides. These findings link functions of immature neutrophils to disease pathogenesis, establishing a clinical cellular signature of GCA and suggesting different therapeutic approaches in systemic vascular inflammation.
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