Kurashima Yosuke, Kunisawa Jun, Higuchi Morio, Gohda Masashi, Ishikawa Izumi, Takayama Naoko, Shimizu Miki, Kiyono Hiroshi
Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
J Immunol. 2007 Aug 1;179(3):1577-85. doi: 10.4049/jimmunol.179.3.1577.
Sphingosine 1-phosphate (S1P) has been proposed as a regulator of lymphocyte trafficking, but its role in mucosa-associated diseases, such as in food allergies, remains to be elucidated. To examine the role of S1P in allergic diseases in the intestine, we used a Th2 cell-mediated Ag-specific allergic diarrhea model and demonstrated that type 1 S1P receptor (S1P(1)) expression was preferentially associated with pathogenic CD4(+) T cells for the development of allergic reactions. Consistent with this demonstration, treatment with FTY720, a modulator of the S1P(1), prevented allergic diarrhea by inhibiting the migration of systemically primed pathogenic CD4(+) T cells induced by oral challenge with allergen into the large intestine. In addition, FTY720 hampered mast cell infiltration into the large intestine, whereas eosinophil infiltration into the large intestine and total and allergen-specific serum IgE production were comparable between mock- and FTY720-treated groups. These results suggest that modulation of the S1P-mediated pathway to inhibit the migration of pathogenic CD4(+) T cells and mast cells into the large intestine could be a novel strategy for preventing allergic diarrhea.
鞘氨醇-1-磷酸（S1P）被认为是淋巴细胞迁移的调节因子，但其在黏膜相关疾病（如食物过敏）中的作用仍有待阐明。为了研究S1P在肠道过敏性疾病中的作用，我们使用了Th2细胞介导的抗原特异性过敏性腹泻模型，并证明1型S1P受体（S1P(1)）的表达与引发过敏反应的致病性CD4(+) T细胞优先相关。与此证明一致，用S1P(1)调节剂FTY720治疗可通过抑制经全身致敏的致病性CD4(+) T细胞在口服过敏原激发后向大肠迁移，从而预防过敏性腹泻。此外，FTY720阻碍肥大细胞浸润至大肠，而在模拟处理组和FTY720处理组之间，嗜酸性粒细胞向大肠的浸润以及血清总IgE和过敏原特异性IgE的产生相当。这些结果表明，调节S1P介导的途径以抑制致病性CD4(+) T细胞和肥大细胞向大肠迁移可能是预防过敏性腹泻的一种新策略。
