Interleukin-27 Receptor Limits Atherosclerosis in Ldlr −/− Mice
| Autor: | Sibylle von Vietinghoff, Mitchell Kronenberg, Gisen Kim, Christiaan J. M. Saris, Klaus Ley, Ekaterina K. Koltsova, Katheleen M. Lloyd |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
CD4-Positive T-Lymphocytes
Male medicine.medical_specialty Chemokine Physiology medicine.medical_treatment Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis Inflammation Article Proinflammatory cytokine Mice Internal medicine medicine Animals Myeloid Cells Receptors Cytokine Aorta Chemokine CCL2 CD11b Antigen biology Tumor Necrosis Factor-alpha Interleukins Interleukin-17 Interleukin Receptors Interleukin Th1 Cells Atherosclerosis Mice Mutant Strains CD11c Antigen Mice Inbred C57BL Endocrinology Cytokine Receptors LDL Immunology biology.protein Interleukin-27 receptor Th17 Cells Female Tumor necrosis factor alpha Interleukin 17 medicine.symptom Cardiology and Cardiovascular Medicine Signal Transduction |
| Zdroj: | Circulation Research. 111:1274-1285 |
| ISSN: | 1524-4571 0009-7330 |
| DOI: | 10.1161/circresaha.112.277525 |
| Popis: | Rationale: Atherosclerosis is a chronic inflammatory disease of the arterial wall. Several proinflammatory cytokines are known to promote atherosclerosis, but less is known about the physiological role of anti-inflammatory cytokines. Interleukin (IL)-27 is a recently discovered member of the IL-6/IL-12 family. The IL-27 receptor is composed of IL-27 receptor A (WSX-1) and gp130 and is required for all established IL-27 signaling pathways. The expression of the IL-27 subunit Ebi3 is elevated in human atheromas, yet its function in atherosclerosis remains unknown. Objective: The aim of this study was to test the role of IL-27 receptor signaling in immune cells in atherosclerosis development. Methods and Results: Atherosclerosis-prone Ldlr −/− mice transplanted with Il27ra −/− bone marrow and fed Western diet for 16 weeks developed significantly larger atherosclerotic lesions in aortic roots, aortic arches, and abdominal aortas. Augmented disease correlated with increased accumulation of CD45 + leukocytes and CD4 + T cells in the aorta, which produced increased amounts of IL-17A and tumor necrosis factor. Several chemokines, including CCL2, were upregulated in the aortas of Ldlr −/− mice receiving Il27ra −/− bone marrow, resulting in accumulation of CD11b + and CD11c + macrophages and dendritic cells in atherosclerotic aortas. Conclusions: The absence of anti-inflammatory IL-27 signaling skews immune responses toward T-helper 17, resulting in increased production of IL-17A and tumor necrosis factor, which in turn enhances chemokine expression and drives the accumulation of proatherogenic myeloid cells in atherosclerotic aortas. These findings establish a novel antiatherogenic role for IL-27 receptor signaling, which acts to suppress the production of proinflammatory cytokines and chemokines and to curb the recruitment of inflammatory myeloid cells into atherosclerotic aortas. |
| Databáze: | OpenAIRE |
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