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      Fermented fish oil suppresses T helper 1/2 cell response in a mouse model of atopic dermatitis via generation of CD4 +CD25 +Foxp3 + T cells

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          Abstract

          Background

          Allergic skin inflammation such as atopic dermatitis (AD), which is characterized by pruritus and inflammation, is regulated partly through the activity of regulatory T cells (Tregs). Tregs play key roles in the immune response by preventing or suppressing the differentiation, proliferation and function of various immune cells, including CD4 + T cells. Recent studies report that fermentation has a tremendous capacity to transform chemical structures or create new substances, and the omega-3 polyunsaturated fatty acids (n-3 PUFAs) in fish oil can reduce inflammation in allergic patients. The beneficial effects of natural fish oil (NFO) have been described in many diseases, but the mechanism by which fermented fish oil (FFO) modulates the immune system and the allergic response is poorly understood. In this study, we produced FFO and tested its ability to suppress the allergic inflammatory response and to activate CD4 +CD25 +Foxp3 + Tregs.

          Results

          The ability of FFO and NFO to modulate the immune system was investigated using a mouse model of AD. Administration of FFO or NFO in the drinking water alleviated the allergic inflammation in the skin, and FFO was more effective than NFO. FFO treatment did increase the expression of the immune-suppressive cytokines TGF-β and IL-10. In addition, ingestion of FFO increased Foxp3 expression and the number of CD4 +CD25 +Foxp3 + Tregs compared with NFO.

          Conclusions

          These results suggest that the anti-allergic effect of FFO is associated with enrichment of CD4 +CD25 + Foxp3 + T cells at the inflamed sites and that FFO may be effective in treating the allergic symptoms of AD.

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          Most cited references30

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          New insights into atopic dermatitis.

          Atopic dermatitis is a chronic inflammatory skin disease associated with cutaneous hyperreactivity to environmental triggers and is often the first step in the atopic march that results in asthma and allergic rhinitis. The clinical phenotype that characterizes atopic dermatitis is the product of interactions between susceptibility genes, the environment, defective skin barrier function, and immunologic responses. This review summarizes recent progress in our understanding of the pathophysiology of atopic dermatitis and the implications for new management strategies.
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            FOXP3: of mice and men.

            The immune system has evolved mechanisms to recognize and eliminate threats, as well as to protect against self-destruction. Tolerance to self-antigens is generated through two fundamental mechanisms: (a) elimination of self-reactive cells in the thymus during selection and (b) generation of a variety of peripheral regulatory cells to control self-reactive cells that escape the thymus. It is becoming increasing apparent that a population of thymically derived CD4+ regulatory T cells, exemplified by the expression of the IL-2Ralpha chain, is essential for the maintenance of peripheral tolerance. Recent work has shown that the forkhead family transcription factor Foxp3 is critically important for the development and function of the regulatory T cells. Lack of Foxp3 leads to development of fatal autoimmune lymphoproliferative disease; furthermore, ectopic Foxp3 expression can phenotypically convert effector T cells to regulatory T cells. This review focuses on Foxp3 expression and function and highlights differences between humans and mice regarding Foxp3 regulation.
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              Regulatory T cells inhibit stable contacts between CD4+ T cells and dendritic cells in vivo

              Regulatory T (T reg) cells exert powerful down-modulatory effects on immune responses, but it is not known how they act in vivo. Using intravital two-photon laser scanning microscopy we determined that, in the absence of T reg cells, the locomotion of autoantigen-specific T cells inside lymph nodes is decreased, and the contacts between T cells and antigen-loaded dendritic cells (DCs) are of longer duration. Thus, T reg cells can exert an early effect on immune responses by attenuating the establishment of stable contacts during priming of naive T cells by DCs.
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                Author and article information

                Contributors
                Journal
                BMC Immunol
                BMC Immunol
                BMC Immunology
                BioMed Central
                1471-2172
                2012
                9 August 2012
                : 13
                : 44
                Affiliations
                [1 ]Department of Pharmacology, School of Medicine, Jeju National University, 66 Jejudaehakno, Jeju, 690-756, South Korea
                [2 ]Fermentec Inc, 207, Jeju Bio industrial Center, 66 Jejudaehakno, Jeju, 690-756, South Korea
                [3 ]Choung Ryong Fisheries Co. LTD, Seogwipo-city, Jeju, 697-943, South Korea
                Article
                1471-2172-13-44
                10.1186/1471-2172-13-44
                3537649
                22873180
                54b77177-e4a9-4c1b-a5d8-1eb04eede9a8
                Copyright ©2012 Han et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 14 March 2012
                : 26 July 2012
                Categories
                Research Article

                Immunology
                Immunology

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