Interruption of the OX40–OX40 Ligand Pathway in LDL Receptor–Deficient Mice Causes Regression of Atherosclerosis
| Autor: | Jason L. Johnson, Gijs H.M. van Puijvelde, Theo J.C. Van Berkel, Hideo Yagita, Amanda C. Foks, Johan Kuiper, Kim L. L. Habets, Ilze Bot, Mariëtte N. D. ter Borg |
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| Rok vydání: | 2013 |
| Předmět: |
Male
medicine.medical_specialty Immunology Antigen-Presenting Cells OX40 Ligand GATA3 Transcription Factor Lymphocyte Activation Immunoglobulin E Lesion Mice chemistry.chemical_compound Th2 Cells Internal medicine medicine Animals Immunology and Allergy Mast Cells Receptor Cells Cultured Cell Proliferation Mice Knockout Membrane Glycoproteins biology Cholesterol business.industry Interleukins Antibodies Monoclonal Receptors OX40 Atherosclerosis Interleukin-33 Mast cell Mice Inbred C57BL B-1 cell Interleukin 33 medicine.anatomical_structure Endocrinology Immunoglobulin M Receptors LDL chemistry Tumor Necrosis Factors LDL receptor biology.protein Interleukin-4 Interleukin-5 medicine.symptom business |
| Zdroj: | The Journal of Immunology. 191:4573-4580 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Patients suffering from cardiovascular disease have well-established atherosclerotic lesions, rendering lesion regression of therapeutic interest. The OX40 (TNFRSF4)–OX40 ligand (OX40L; TNFSF4) pathway is important for the proliferation and survival of T cells, stimulates B cells, and is associated with cardiovascular disease. We hypothesized that interference with the OX40–OX40L pathway, in combination with decreases in cholesterol, may induce regression of atherosclerosis. LDLr−/− mice were fed a Western-type diet for 10 wk, after which they received chow diet and were treated with anti-OX40L or PBS for 10 wk. A significant regression of lesions was observed in the aorta and aortic arch of anti-OX40L–treated mice compared with control mice. Interference of the OX40–OX40L pathway reduced Th2 responses, as shown by decreases in GATA-3 and IL-4 levels. Also, IgE levels were decreased, as demonstrated by reduced mast cell presence and activation. Notably, IL-5 production by T and B1 cells was increased, thus enhancing atheroprotective oxidized low-density lipoprotein–specific IgM production. The increase in IL-5 production and IgM was mediated by IL-33 production by APCs upon OX40L blockade. We conclude that interruption of the OX40–OX40L signaling pathway, combined with decreases in dietary cholesterol, induces the regression of atherosclerosis through induction of IL-5–producing T cells and oxidized low-density lipoprotein–specific IgM and reductions in Th2 and mast cells. |
| Databáze: | OpenAIRE |
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