Effects of zinc deficient diet on development of atopic dermatitis-like eruptions in DS-Nh mice.
ABSTRACT Zinc is one of the essential dietary factors and zinc deficiency diminishes the immune system. However, the mechanisms by which zinc deficiency affects the immune system are not fully understood.
We analyzed the mechanisms of zinc deficiency affecting the allergic response using a DS-Nh mouse model of atopic dermatitis.
Male DS-Nh mice were fed a zinc deficient diet for 4 weeks. We measured transepidermal water loss (TEWL) and epidermal moisture level, assessed the skin eruption score, and examined the frequency of lymphocyte subpopulation in spleen and thymus by flow cytometry. The suppressive effect of CD25+CD4+ T cells was analyzed in vitro. The amount of cytokines produced by the spleen cells and the serum IgE levels were measured by ELISA.
In DS-Nh mice fed the zinc deficient diet, skin eruptions were exacerbated and serum IgE levels and number of S. aureus on the skin surface was increased. IFN-gamma and IL-13 production by spleen cells was increased. The number of CD25+CD4+ T cells in spleen was significantly decreased, while the percentage of Foxp3 positive cells in the CD25+CD4+ T cells was comparable to those of the controls. CD25+CD4+ T cells from mice fed the zinc deficient diet maintained a suppressive function compared with those from the controls.
These findings indicate that zinc deficiency influences the skin barrier system and immune system, and suggests that zinc deficiency acts as an exacerbation factor of atopic dermatitis.
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ABSTRACT: DS-Nh (DS Nh/+) mice spontaneously develop dermatitis when they are housed in a conventional environment. In this study, we analyzed the clinical and histopathological features of dermatitis in DS-Nh mice, which is characterized by erythema, edema, and erosion on the face, neck, chest and flexor surfaces of their forelegs with marked scratching behavior. Histopathological examination, including immunohistochemistry, revealed that inflammatory cells consisting of mast cells, eosinophils, CD4-positive T cell-dominant lymphocytes and CD11b-positive macrophages infiltrated the skin lesions. The cytokine production pattern of inflammatory cells in a lesional skin tissue was shifted to the Th2-type (IL-4) rather than the Th1 type (IFN-gamma). Serum IgE levels were elevated and correlated with the severity of the clinical skin conditions. These skin symptoms were observed in association with a colonization of Staphylococcus aureus. Similar clinical and histopathological symptoms were inducible with repeated percutaneous immunization of heat-killed S. aureus on the back of SPF DS-Nh mice. These results suggest that the spontaneous dermatitis that occurs in conventionally raised DS-Nh mice is comparable to a certain type of human atopic dermatitis (AD), which is associated with S. aureus, a recognized environmental factor. Thus, we consider that DS-Nh mice offer a useful model for investigating the pathogenesis of AD and for developing new therapeutic approaches or drugs for treating AD.Journal of Dermatological Science 12/2002; 30(2):142-53. · 3.52 Impact Factor
- Journal of Allergy and Clinical Immunology - J ALLERG CLIN IMMUNOL. 01/1991; 87(6):1088-1095.
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ABSTRACT: It is well known that cyclophosphamide (Cy) treatment before sensitization paradoxically enhances rather than suppresses contact hypersensitivity (CH) reactions. In fact, Cy-treated mice developed a significant (p < 0.05) increase of the CH reactions to 2,4,6-trinitro-1-chrolobenzene (TNCB) in comparison with untreated mice. In order to examine whether the target cells of Cy in the immuno-augmentative effect are CD25(+) CD4(+) regulatory T cells or not, we investigated effect of Cy treatment on CD25(+) CD4(+) T cells. We examined Cy-treated CD25(+) CD4(+) T cells by flow cytometer and by inhibition assay on proliferation of CD25(-) CD4(+) T cells. Cy treatment remarkably reduced the number and percentage of CD25(+) CD4(+) T cells in the spleen and lymph nodes 3 and 5 days later. Moreover, CD25(+) CD4(+) T cells taken from the Cy-treated mice 3 days later showed the lower suppressive activity on proliferation of CD25(-) CD4(+) T cells, as compared to that from the untreated mice. Furthermore, transfer of CD25(+) CD4(+) T cells from untreated mice resulted in a significant decrease (p < 0.05) of the CH reactions enhanced by Cy treatment. These results indicate that enhancement of the CH reactions to TNCB by Cy treatment is attributed to the decrease in the number, percentage and the function of CD25(+) CD4(+) regulatory T cells.Journal of Dermatological Science 08/2005; 39(2):105-12. · 3.52 Impact Factor