n−3 PUFA (polyunsaturated fatty acids), i.e. DHA (docosahexaenoic acid), found in fish oil, exhibit anti-inflammatory properties; however, the molecular mechanisms remain unclear. Since PtdIns(4,5)P2 resides in raft domains and DHA can alter the size of rafts, we hypothesized that PtdIns(4,5)P2 and downstream actin remodelling are perturbed by the incorporation of n−3 PUFA into membranes, resulting in suppressed T-cell activation. CD4+ T-cells isolated from Fat-1 transgenic mice (membranes enriched in n−3 PUFA) exhibited a 50% decrease in PtdIns(4,5)P2. Upon activation by plate-bound anti-CD3/anti-CD28 or PMA/ionomycin, Fat-1 CD4+ T-cells failed to metabolize PtdIns(4,5)P2. Furthermore, actin remodelling failed to initiate in Fat-1 CD4+ T-cells upon stimulation; however, the defect was reversed by incubation with exogenous PtdIns(4,5)P2. When Fat-1 CD4+ T-cells were stimulated with anti-CD3/anti-CD28-coated beads, WASP (Wiskott–Aldrich syndrome protein) failed to translocate to the immunological synapse. The suppressive phenotype, consisting of defects in PtdIns(4,5)P2 metabolism and actin remodelling, were recapitulated in CD4+ T-cells isolated from mice fed on a 4% DHA triacylglycerol-enriched diet. Collectively, these data demonstrate that n−3 PUFA, such as DHA, alter PtdIns(4,5)P2 in CD4+ T-cells, thereby suppressing the recruitment of WASP to the immunological synapse, and impairing actin remodelling in CD4+ T-cells.
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Research Article|
March 14 2012
n−3 polyunsaturated fatty acids suppress phosphatidylinositol 4,5-bisphosphate-dependent actin remodelling during CD4+ T-cell activation
Tim Y. Hou;
Tim Y. Hou
*Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas, U.S.A.
†Program in Integrative Nutrition and Complex Diseases, Texas A&M University, College Station, Texas, U.S.A.
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Jennifer M. Monk;
Jennifer M. Monk
†Program in Integrative Nutrition and Complex Diseases, Texas A&M University, College Station, Texas, U.S.A.
‡Texas AgriLife Vegetable Crop Improvement Center, Texas A&M University, College Station, Texas, U.S.A.
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Yang-Yi Fan;
Yang-Yi Fan
†Program in Integrative Nutrition and Complex Diseases, Texas A&M University, College Station, Texas, U.S.A.
‡Texas AgriLife Vegetable Crop Improvement Center, Texas A&M University, College Station, Texas, U.S.A.
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Rola Barhoumi;
Rola Barhoumi
§Center for Environmental and Rural Health, Texas A&M University, College Station, Texas, U.S.A.
∥Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, Texas, U.S.A.
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Yong Q. Chen;
Yong Q. Chen
¶Department of Cancer Biology, Wake Forest University, Winston-Salem, NC, U.S.A.
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Gonzalo M. Rivera;
Gonzalo M. Rivera
**Department of Veterinary Pathobiology, Texas A&M University, College Station, Texas, U.S.A.
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David N. McMurray;
David N. McMurray
†Program in Integrative Nutrition and Complex Diseases, Texas A&M University, College Station, Texas, U.S.A.
‡Texas AgriLife Vegetable Crop Improvement Center, Texas A&M University, College Station, Texas, U.S.A.
§Center for Environmental and Rural Health, Texas A&M University, College Station, Texas, U.S.A.
∥Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, Texas, U.S.A.
††Faculty of Nutrition, Texas A&M University, College Station, Texas, U.S.A.
§§Department of Microbial and Molecular Pathogenesis, Texas A&M University System Health Science Center, Texas A&M University, College Station, Texas, U.S.A.
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Robert S. Chapkin
Robert S. Chapkin
1
*Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas, U.S.A.
†Program in Integrative Nutrition and Complex Diseases, Texas A&M University, College Station, Texas, U.S.A.
‡Texas AgriLife Vegetable Crop Improvement Center, Texas A&M University, College Station, Texas, U.S.A.
§Center for Environmental and Rural Health, Texas A&M University, College Station, Texas, U.S.A.
∥Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, Texas, U.S.A.
††Faculty of Nutrition, Texas A&M University, College Station, Texas, U.S.A.
1To whom correspondence should be addressed (email r-chapkin@tamu.edu).
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Publisher: Portland Press Ltd
Received:
August 31 2011
Revision Received:
December 22 2011
Accepted:
January 18 2012
Accepted Manuscript online:
January 18 2012
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2012 Biochemical Society
2012
Biochem J (2012) 443 (1): 27–37.
Article history
Received:
August 31 2011
Revision Received:
December 22 2011
Accepted:
January 18 2012
Accepted Manuscript online:
January 18 2012
Citation
Tim Y. Hou, Jennifer M. Monk, Yang-Yi Fan, Rola Barhoumi, Yong Q. Chen, Gonzalo M. Rivera, David N. McMurray, Robert S. Chapkin; n−3 polyunsaturated fatty acids suppress phosphatidylinositol 4,5-bisphosphate-dependent actin remodelling during CD4+ T-cell activation. Biochem J 1 April 2012; 443 (1): 27–37. doi: https://doi.org/10.1042/BJ20111589
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