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BACKGROUND AND PURPOSE In recent years, the incidence of allergic diseases, especially food allergies (food allergy, FA) in the global rapid increase about 2% to 6% of people have food allergies and related symptoms. FA symptoms ranging from performance as vomiting, diarrhea, discomfort, difficulty breathing, rashes and other life-threatening anaphylactic shock. In recent years the field of food allergy research progress rapidly, but its pathogenesis remains unclear, the prevailing FA tolerance between the intestinal immune system and food antigens balance is broken, to Th2 cell response. immune response. Under normal circumstances, the intestinal immune system to food antigens and intestinal commensal bacteria can produce tolerance and integrity of the intestinal epithelium, dendritic cells (dendritic cell, DC) and regulatory T cells and the like to maintain this balance to important. CD4 CD25 - regulatory T (Treg) cells to regulate a subtype of T cells play an important role in the anti-infection, transplantation tolerance, oral tolerance and autoimmune disease, will lead to intestinal dysfunction or decline in the number of Road imbalance of immune tolerance. Murine and human Treg can selectively expressed prongs wing helix transcription factor (Foxp3) expression of Foxp3 Treg cells role in the maintenance of immune tolerance has been confirmed, the Foxp3 gene mutations or decreased expression of Treg cells can lead to dysfunction . However, Treg functional status in the FA and the mechanism of action is still not clear. T cell immunoglobulin and mucin domain protein (T cell immunoglobulin and mucin domains, TIMS) 2001 was first discovered in mice, including TIM1-TIM8, in the human genome have been found in the homologous similar molecules (TIM1, TIM3 TIM4). TIMS family gene polymorphism and autoimmune diseases, allergic diseases and Th1-Th2 cell balance between the role of people's attention. CD4 T cells in mice Expression TIM1, TIM4 is, its ligand expression in mature DC, high expression TIM4 of TIM1 binding can break the Th1-Th2 cell balance, to promote Th2 cytokine release, and generates the corresponding inflammatory reaction. TIM1 in regulating Treg function also shows an important role, in vitro experiments have confirmed a TIM1 the activation can be reduced Treg cell Foxp3, glucocorticoid-induced tumor necrosis factor receptor (glucocorticoid-induced tumor necrosis factor receptor, GITR) and other Treg cell surface molecules of mRNA and function. Treg functional status in the FA and the TIM1 its impact has not been reported, we hypothesized that the FA Treg cell dysfunction, TIM4 TIM1 interaction may reduce the function and status of Treg cells, destroying the balance of immune tolerance, It is one of the important mechanisms causing the FA. This study by constructing Staphylococcus aureus enterotoxin B (staphylococcal enterotoxin B, SEB) ovalbumin (ovalbumin, OVA) food allergy mouse model detection the FA state of Treg function and TIM1 antibody, and TIM4 antibody intervention, TIM1 Treg function and the pathogenesis of the FA do further exploration. SEB and OVA-sensitized BALB / c mouse model, through the determination of the the mice jejunum and the spleen of Foxp3 mRNA expression of TGF-beta1 and IL-10 inhibition of cytokine levels, about the functional status of Treg in the FA; TIM1 to use and TIM4 antibody intervention study in the FA TIM4-the TIM1 path of Treg function. 32 Materials and Methods test protein feeding BALB / c mice were randomly divided into four groups: control group, the SEB OVA common action group, TIM1 antibody intervention group, TIM4 antibody intervention group, respectively 0,3,9 intraperitoneal injection of saline, SEB and OVA, the TIM1 Antibody SEB OVA, TIM4 antibody SEB OVA, and in the 7th and 14th day to SEB OVA (blank control group fed saline). Diarrhea in mice modeling a sign of success, if sensitized mice does not appear to significantly diarrhea, observed the mice were sacrificed and intestinal contents, stool samples relative to the ball in the normal mouse colon, watery stool may also be considered as diarrhea. Mice were sacrificed 24 hours after last gavage, and the detection of the relevant indicators. 1 ELISA method for the determination of serum OVA SiGe with IL-4, RT-PCR detection of the jejunum and the spleen Foxp3 mRNA expression. 3 RT-PCR detection jejunum and TIM4 has mRNA expression. 4 ELISA method for the determination of serum TGF-beta 1 and IL-10 Immunohistochemistry was used to detect jejunal mucosal TGF-beta 1 and IL-10 expression. 6 He dyeing detect the number of jejunal mucosal eosinophils. The resulting data were analyzed by SPSS13.0 statistical package for analysis. The mean between the two groups compared using one-way ANOVA to alpha = 0.05 for hypothesis testing standards. 1 compared with the control group mice, SEB OVA allergic mice OVA SiGe (P lt; 0.05) and IL-4 (P lt; 0.05) significantly increased eosinophils increased significantly (P lt; 0.05) . 2 mice compared with the control group, the SEB OVA allergic mice jejunum and spleen Foxp3 expression was significantly reduced (0.401 ± 0.145 vs 0.732 ± 0.162, P = 0.000; 0.407 ± 0.082 vs 0.691 ± 0.145, P = 0.000), TIM1 and intervene in TIM4 antibody group jejunum and spleen Foxp3 expression of allergic mice was significantly restored (P are lt; 0.05), close to the control group. Compared with the control group of mice (0.485) the SEB OVA (0.615), of TIM1 (0.606) and TIM4 (0.578) antibody intervention mice TIM4 expression (P = 0.004, P = 0.007, P = 0.033) expression was no significant difference between the antibody intervention group. Compared with the control group mice, SEB OVA allergic mice serum and jejunum TGF-beta1 (7859.853 ± 126.704 vs. 8342.814 ± 488.461, P lt; 0.05; 108.834 ± 9.634 vs. 156.298 ± 12.002, P lt; 0.05) expression significantly reduced the TIM1 and TIM4 antibody Intervention group and jejunum of TGF-beta1 allergic mice was restored (P are lt; 0.05) SEB OVA allergic mice TIM1 and TIM4, antibody intervention group OVA SiGe and IL-4 was restored, the number of eosinophils decreased (P are lt; 0.05), close with the control group. Conclusion 1 SEB OVA stimulation can promote the mice food allergies occur. SEB OVA allergic mice jejunum and spleen Foxp3 expression was decreased, and the presence of serum, and jejunum TGF-beta1 expression decreased, suggesting that allergic the mice presence of regulatory T cell dysfunction, Treg function insufficiency from the in mice food allergy in effect. 3 SEB OVA stimulation promote mouse TIM4 expression increased. Antibodies TIM1 and TIM4 of intervention can improve the function of Treg, improve allergy symptoms prompted the TIM1-TIM4 pathway play an important role in the mice food allergy.
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