n-3 Polyunsaturated Fatty Acids Suppress Mitochondrial Translocation to the Immunologic Synapse and Modulate Calcium Signaling in T Cells
| Autor: | Rajeshwari Yog, Robert S. Chapkin, David N. McMurray, Rola Barhoumi |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
CD4-Positive T-Lymphocytes
Immunological Synapses T cell Immunology Antigen-Presenting Cells Mice Transgenic Cell Communication Mitochondrion Biology Lymphocyte Activation Article Immunological synapse Mitochondrial Proteins Mice Fatty Acids Omega-3 Immune Tolerance medicine Animals Immunology and Allergy Calcium Signaling Antigen-presenting cell Uniporter Calcium signaling Hybridomas Wild type Coculture Techniques Cell biology Mice Inbred C57BL Protein Transport medicine.anatomical_structure Cell activation |
| Zdroj: | The Journal of Immunology. 184:5865-5873 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Recent studies indicate that the process of Ag presentation induces cytoskeleton-dependent mitochondrial redistribution to the immediate vicinity of the immunologic synapse (IS). This redistribution of mitochondria to the IS in T cells is necessary to maintain Ca2+ influx and Th cell activation. Recently, we demonstrated that n-3 polyunsaturated fatty acids (PUFAs) suppress the localization and activation of signaling proteins at the IS. Therefore, we hypothesized that n-3 PUFAs suppress CD4+ T cell mitochondrial translocation during the early stages of IS formation and downmodulate Ca2+-dependent Th cell activation. CD4+ cells derived from fat-1 mice, a transgenic model that synthesizes n-3 PUFA from n-6 PUFA, were cocultured with anti-CD3–expressing hybridoma cells (145-2C11) for 15 min at 37°C, and mitochondrial translocation to the IS was assessed by confocal microscopy. Fat-1 mice exhibited a significantly (p < 0.05) reduced percentage of T cells with mitochondria which translocated to the IS; fat-1 (30%) versus wild type control (82%). Regarding the effect on the mitochondrial-to-cytosolic Ca2+ ratio, wild type cells showed significant increases at the IS (71%) and total cell (60%) within 30 min of IS formation. In contrast, fat-1 CD4+ T cells remained at basal levels following the IS formation. A similar blunting of the mitochondrial-to-cytosolic Ca2+ ratio was observed in wild type cells that were coincubated with inhibitors of the mitochondrial uniporter, RU360 or calcium release-activated Ca2+ (CRAC) channels, BTP2. These observations provide evidence that n-3 PUFAs modulate Th cell activation by limiting mitochondrial translocation to the IS and reducing Ca2+entry. |
| Databáze: | OpenAIRE |
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