T-Cell Immunoglobulin and Mucin Domain 3 Acts as a Negative Regulator of Atherosclerosis
| Autor: | Gijs H.M. van Puijvelde, Loes Wasserman, Ingrid A. Ran, Hisaya Akiba, Vanessa Frodermann, Peter J. van Santbrink, Hideo Yagita, Amanda C. Foks, Johan Kuiper, Saskia C.A. de Jager, Mariëtte N. D. ter Borg, Ilze Bot |
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| Rok vydání: | 2013 |
| Předmět: |
Pathology
medicine.medical_specialty T cell Apoptosis Inflammation T-Lymphocytes Regulatory Monocytes Negative regulator Mice Interleukin 21 medicine Animals IL-2 receptor Antibodies Blocking Hepatitis A Virus Cellular Receptor 2 Aorta Mice Knockout B-Lymphocytes Regulatory biology Macrophages Mucin Atherosclerosis Plaque Atherosclerotic Cell biology medicine.anatomical_structure biology.protein Receptors Virus Arterial blood Antibody medicine.symptom Cardiology and Cardiovascular Medicine Signal Transduction |
| Zdroj: | Arteriosclerosis, Thrombosis, and Vascular Biology. 33:2558-2565 |
| ISSN: | 1524-4636 1079-5642 |
| Popis: | Objective— Atherosclerosis is a chronic autoimmune-like disease in which lipids and fibrous elements accumulate in the arterial blood vessels. T cells are present within atherosclerotic plaques, and their activation is partially dependent on costimulatory signals, which can either provide positive or negative signals that promote T-cell activation or limit T-cell responses, respectively. T-cell immunoglobulin and mucin domain 3 (Tim-3) is a coinhibitory type 1 transmembrane protein that affects the function of several immune cells involved in atherosclerosis, such as monocytes, macrophages, effector T cells, and regulatory T cells. In the present study, we determined the role of Tim-3 in the development of atherosclerosis. Approach and Results— Western-type diet–fed low-density lipoprotein receptor–deficient (LDLr −/− ) mice were treated with an anti–Tim-3 antibody for 3 and 8 weeks. Anti–Tim-3 administration increased fatty streak formation with 66% and increased atherosclerotic plaque formation after 8 weeks with 35% in the aortic root and with 50% in the aortic arch. Furthermore, blockade of Tim-3 signaling increased percentages of circulating monocytes with 33% and lesional macrophages with 20%. In addition, anti–Tim-3 administration increased CD4 + T cells with 17%, enhanced their activation status, and reduced percentages of regulatory T cells with 18% and regulatory B cells with 37%. Conclusions— It is known that Tim-3 acts as a negative regulator of both innate and adaptive immune responses, and in the present study, we show that anti–Tim-3 treatment augments lesion development, accompanied by an increase in the number of monocytes/macrophages and CD4 + T cells and by decreased regulatory T cells and regulatory B cells. |
| Databáze: | OpenAIRE |
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