ArticleArthritis & rheumatology (Hoboken, N.J.)2021
A Distinct Macrophage Subset Mediating Tissue Destruction and Neovascularization in Giant Cell Arteritis: Implication of the YKL-40/Interleukin-13 Receptor α2 Axis.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- Chitinase‑3 like‑protein‑1: A potential predictor of cardiovascular disease (Review).Molecular medicine reports · 2024Pooled it
- CHI3L1: a novel regulator of vascular remodeling in pulmonary arterial hypertension.Molecular and cellular biochemistry · 2026Article
- Diagnostic Challenges and Modern Therapeutic Strategies in Giant Cell Arteritis.Diagnostics (Basel, Switzerland) · 2026Review
- Monocytes/Macrophages in Giant Cell Arteritis-Polymyalgia Rheumatica Spectrum Disease.Aging and disease · 2025Review
- Dynamic macrophage phenotypes in autoimmune and inflammatory rheumatic diseases.Nature reviews. Rheumatology · 2025Review
- Trans-omics landscape of systemic vasculitis identified matrix metalloproteinase 12 as a novel signature molecule.Rheumatology (Oxford, England) · 2025Article
- Implications of Chitinase 3-like 1 Protein in the Pathogenesis of Multiple Sclerosis in Autopsied Brains and a Murine Model.International journal of molecular sciences · 2025Article
- Associations between plasma metabolism-associated proteins and future development of giant cell arteritis: results from a prospective study.Rheumatology (Oxford, England) · 2025Article
- Inflammatory Effects and Regulatory Mechanisms of Chitinase-3-like-1 in Multiple Human Body Systems: A Comprehensive Review.International journal of molecular sciences · 2024Review
- Uncovering novel mechanisms of chitinase-3-like protein 1 in driving inflammation-associated cancers.Cancer cell international · 2024Review
- Immune checkpoints in autoimmune vasculitis.Best practice & research. Clinical rheumatology · 2024Review
- Review
- Review
- [Role and mechanisms of CHI3L1 in coronary artery lesions in a mouse model of Kawasaki disease-like vasculitis].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2023Article
- Frailty is related to serum inflammageing markers: results from the VITAL study.Immunity & ageing : I & A · 2023Article
- Potential Roles and Future Perspectives of Chitinase 3-like 1 in Macrophage Polarization and the Development of Diseases.International journal of molecular sciences · 2023Review
- Disease stratification in GCA and PMR: state of the art and future perspectives.Nature reviews. Rheumatology · 2023Review
- Immunology of Giant Cell Arteritis.Circulation research · 2023Review
- Biomarkers in the era of targeted therapy in giant cell arteritis and polymyalgia rheumatica: is it possible to replace acute-phase reactants?Frontiers in immunology · 2023Review
- Exploring the causal role of gut microbiota in giant cell arteritis: a Mendelian randomization analysis with mediator insights.Frontiers in immunology · 2023Article
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Authors and funding
9 authors at 1 institution in 2 countries.
Funding
Abstract
objectiveMacrophages mediate inflammation, angiogenesis, and tissue destruction in giant cell arteritis (GCA). Serum levels of the macrophage-associated protein YKL-40 (chitinase 3-like protein 1), previously linked to angiogenesis and tissue remodeling, remain elevated in GCA despite glucocorticoid treatment. This study was undertaken to investigate the contribution of YKL-40 to vasculopathy in GCA.
methodsImmunohistochemistry was performed on GCA temporal artery biopsy specimens (n = 12) and aortas (n = 10) for detection of YKL-40, its receptor interleukin-13 receptor α2 (IL-13Rα2), macrophage markers PU.1 and CD206, and the tissue-destructive protein matrix metalloproteinase 9 (MMP-9). Ten noninflamed temporal artery biopsy specimens served as controls. In vitro experiments with granulocyte-macrophage colony-stimulating factor (GM-CSF)- or macrophage colony-stimulating factor (M-CSF)-skewed monocyte-derived macrophages were conducted to study the dynamics of YKL-40 production. Next, small interfering RNA-mediated knockdown of YKL-40 in GM-CSF-skewed macrophages was performed to study its effect on MMP-9 production. Finally, the angiogenic potential of YKL-40 was investigated by tube formation experiments using human microvascular endothelial cells (HMVECs).
resultsYKL-40 was abundantly expressed by a CD206+MMP-9+ macrophage subset in inflamed temporal arteries and aortas. GM-CSF-skewed macrophages from GCA patients, but not healthy controls, released significantly higher levels of YKL-40 compared to M-CSF-skewed macrophages (P = 0.039). In inflamed temporal arteries, IL-13Rα2 was expressed by macrophages and endothelial cells. Functionally, knockdown of YKL-40 led to a 10-50% reduction in MMP-9 production by macrophages, whereas exposure of HMVECS to YKL-40 led to significantly increased tube formation.
conclusionIn GCA, a GM-CSF-skewed, CD206+MMP-9+ macrophage subset expresses high levels of YKL-40 which may stimulate tissue destruction and angiogenesis through IL-13Rα2 signaling. Targeting YKL-40 or GM-CSF may inhibit macrophages that are currently insufficiently suppressed by glucocorticoids.
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