Docosahexaenoic acid reduces suppressive and migratory functions of CD4+CD25+ regulatory T-cells.

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 Res

authors

Yessoufou A,Plé A,Moutairou K,Hichami A,Khan NA

doi

10.1194/jlr.M900101-JLR200

subject

Has Abstract

pub_date

2009-12-01 00:00:00

pages

2377-88

issue

12

eissn

0022-2275

issn

1539-7262

pii

M900101-JLR200

journal_volume

50

pub_type

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