NDLI: n−3 Polyunsaturated Fatty Acids Suppress Mitochondrial Translocation to the Immunologic Synapse and Modulate Calcium Signaling in T Cells

Content Provider	PubMed Central
Author	Yog, Rajeshwari Barhoumi, Rola Mcmurray, David N. Chapkin, Robert S.
Copyright Year	2010
Abstract	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.
Related Links	http://dx.doi.org/10.4049/jimmunol.0904102
Ending Page	5873
Page Count	9
Starting Page	5865
File Format	PDF
ISSN	15506606
e-ISSN	15506606
Journal	Journal of immunology (Baltimore, Md. : 1950)
Issue Number	10
Volume Number	184
Language	English
Publisher Date	2010-05-15
Access Restriction	Open
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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