Abstract:
:Immunological tolerance is one of the fundamental aspects of the immune system. The CD4(+)CD25(+) regulatory T (Treg) cells have emerged as key players in the development of tolerance to self and foreign antigens. However, little is known about the endogenous factors and mechanisms controlling their suppressive capacity on immune response. In this study, we observed that docosahexaenoic acid (DHA), an n-3 polyunsaturated fatty acid, diminished, in a dose-dependent manner, the capacity of Treg cells to inhibit the CD4(+)CD25(-) effector T-cell proliferation. DHA not only reduced the migration of Treg cells toward chemokines but also downregulated the mRNA expression of CCR-4 and CXCR-4 in Treg cells. DHA also curtailed ERK1/2 and Akt phosphorylation and downregulated the Smad7 levels in these cells. Contradictorily, DHA upregulated the mRNA expression of Foxp3, CTLA-4, TGF-beta, and IL-10; nonetheless, this fatty acid increased the expression of p27(KIP1) mRNA, known to be involved in Treg cell unresponsiveness. In Foxp3-immunoprepitated nuclear proteins, DHA upregulated histone desacetylase 7 levels that would again participate in the unresposnsiveness of these cells. Finally, a DHA-enriched diet also diminished, ex vivo, the suppressive capacity of Treg cells. Altogether, these results suggest that DHA, by diminishing Treg cell functions, may play a key role in health and disease.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Yessoufou A,Plé A,Moutairou K,Hichami A,Khan NAdoi
10.1194/jlr.M900101-JLR200subject
Has Abstractpub_date
2009-12-01 00:00:00pages
2377-88issue
12eissn
0022-2275issn
1539-7262pii
M900101-JLR200journal_volume
50pub_type
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journal_title:Journal of lipid research
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journal_title:Journal of lipid research
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更新日期:1980-11-01 00:00:00
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journal_title:Journal of lipid research
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pub_type: 杂志文章,评审
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更新日期:2002-12-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章,评审
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pub_type: 杂志文章
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journal_title:Journal of lipid research
pub_type: 杂志文章
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更新日期:1997-04-01 00:00:00
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pub_type: 杂志文章
doi:
更新日期:1993-05-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1973-07-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1984-10-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1994-11-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1990-09-01 00:00:00
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journal_title:Journal of lipid research
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journal_title:Journal of lipid research
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更新日期:2002-06-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章
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journal_title:Journal of lipid research
pub_type: 杂志文章
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更新日期:1980-02-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章
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