Immunology Program, Benaroya Research Institute, Seattle, Washington, USA.
Division of Allergy and Infectious Diseases, University of Washington School of Medicine, Seattle, Washington, USA.
Mucosal Immunol. 2018 Mar;11(2):394-403. doi: 10.1038/mi.2017.61. Epub 2017 Jun 28.
Atopic dermatitis (AD) often precedes asthma and food allergy, indicating that epicutaneous sensitization to allergens may be important in the induction of allergic responses at other barrier surfaces. Thymic stromal lymphopoietin (TSLP) and interleukin (IL)-33 are two cytokines that may drive type 2 responses in the skin; both are potential targets in the treatment of allergic diseases. We tested the functional role of IL-33 and the interplay between IL-33 and TSLP in mouse models of atopic march and gastrointestinal (GI) allergy. IL-33-driven allergic disease occurred in a TSLP-independent manner. In contrast, mice lacking IL-33 signaling were protected from onset of allergic diarrhea in TSLP-driven disease. Epithelial-derived IL-33 was important in this model, as specific loss of IL-33 expression in the epithelium attenuated cutaneous inflammation. Notably, the development of diarrhea following sensitization with TLSP plus antigen was ameliorated even when IL-33 was blocked after sensitization. Thus, IL-33 has an important role during early cutaneous inflammation and during challenge. These data reveal critical roles for IL-33 in the "atopic march" that leads from AD to GI allergy.
特应性皮炎（AD）常先于哮喘和食物过敏发生，这表明过敏原的经皮致敏可能在其他屏障表面的过敏反应诱导中起重要作用。胸腺基质淋巴细胞生成素（TSLP）和白细胞介素（IL）-33 是两种可能在皮肤中驱动 2 型反应的细胞因子；它们都是治疗过敏疾病的潜在靶点。我们在特应性进行曲和胃肠道（GI）过敏的小鼠模型中测试了 IL-33 和 IL-33 与 TSLP 之间相互作用的功能作用。IL-33 驱动的过敏性疾病发生在 TSLP 独立的方式中。相比之下，缺乏 IL-33 信号的小鼠在 TSLP 驱动的疾病中免受过敏性腹泻的发生。上皮衍生的 IL-33 在该模型中很重要，因为上皮细胞中 IL-33 表达的特异性缺失减弱了皮肤炎症。值得注意的是，即使在致敏后阻断 IL-33 后，用 TSLP 加抗原致敏后腹泻的发展也得到了改善。因此，IL-33 在早期皮肤炎症和挑战期间都起着重要作用。这些数据揭示了 IL-33 在导致从 AD 到 GI 过敏的“特应性进行曲”中的关键作用。
