Miyata Masanori, Hatsushika Kyosuke, Ando Takashi, Shimokawa Naomi, Ohnuma Yuko, Katoh Ryohei, Suto Hajime, Ogawa Hideoki, Masuyama Keisuke, Nakao Atsuhito
Department of Immunology, University of Yamanashi Faculty of Medicine, Yamanashi, Japan.
Eur J Immunol. 2008 Jun;38(6):1487-92. doi: 10.1002/eji.200737809.
Epithelial cell-derived thymic stromal lymphopoietin (TSLP) is a master switch for asthma or atopic dermatitis by inducing a dendritic cell-mediated Th2-type allergic inflammation. Allergic rhinitis is also pathologically characterized by Th2-type allergic inflammation. This study demonstrates that mast cells regulate the epithelial TSLP expression in allergic rhinitis. TSLP expression was found to be up-regulated predominantly in the nasal epithelium in the ovalbumin (OVA)-sensitized and -nasally challenged mouse model of allergic rhinitis, which was abolished in mast cell-deficient WBB6F1-W/W(v) in comparison with control WBB6F1-+/+ mice. Similarly, the epithelial TSLP expression was reduced in Fc receptor gamma chain (FcgammaR)-deficient mice, where the high-affinity IgE receptor (FcepsilonRI) is not expressed on mast cells, in comparison with control C57BL/6 mice. Furthermore, the administration of neutralizing TSLP antibody during the challenge phase of OVA inhibited the development of allergic rhinitis. These results suggest that the direct stimulation of epithelial cells by antigens alone may not be sufficient to induce TSLP expression in the nasal epithelium, and that mast cell regulation of epithelial TSLP expression, possibly via FcepsilonRI, plays an important role in the development of allergic rhinitis.
上皮细胞源性胸腺基质淋巴细胞生成素（TSLP）是哮喘或特应性皮炎的主要开关，可诱导树突状细胞介导的2型过敏性炎症。变应性鼻炎的病理特征也是2型过敏性炎症。本研究表明，肥大细胞在变应性鼻炎中调节上皮TSLP的表达。在卵清蛋白（OVA）致敏和经鼻激发的变应性鼻炎小鼠模型中，发现TSLP表达主要在鼻上皮中上调，与对照WBB6F1-+/+小鼠相比，在肥大细胞缺陷的WBB6F1-W/W(v)小鼠中该上调被消除。同样，与对照C57BL/6小鼠相比，在Fc受体γ链（FcgammaR）缺陷小鼠中上皮TSLP表达降低，在该小鼠中肥大细胞上不表达高亲和力IgE受体（FcepsilonRI）。此外，在OVA激发阶段给予中和性TSLP抗体可抑制变应性鼻炎的发展。这些结果表明，仅抗原对上皮细胞的直接刺激可能不足以诱导鼻上皮中TSLP的表达，并且肥大细胞对上皮TSLP表达的调节（可能通过FcepsilonRI）在变应性鼻炎的发展中起重要作用。
