IL-33 promotes gastrointestinal allergy in a TSLP-independent manner.
IL-33 promotes gastrointestinal allergy in a TSLP-independent manner.
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DOI：
10.1038/mi.2017.61
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发表时间：
2018-03
影响因子：
8
通讯作者：
Ziegler SF
中科院分区：
文献类型：
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作者：
Han H;Roan F;Johnston LK;Smith DE;Bryce PJ;Ziegler SF
特应性皮炎（AD）通常先于哮喘和食物过敏，这表明对过敏原的表皮致敏可能在诱导其他屏障表面的过敏反应中很重要。胸腺基质淋巴生成素（TSLP）和IL-33是两种可能驱动皮肤2型反应的细胞因子；两者都是治疗过敏性疾病的潜在靶点。我们在小鼠特应性进行和胃肠道变态反应模型中检测了IL-33的功能作用以及IL-33与TSLP的相互作用。il -33驱动的过敏性疾病以不依赖于tslp的方式发生。相反，缺乏IL-33信号的小鼠在tslp驱动的疾病中免于过敏性腹泻的发作。上皮来源的IL-33在该模型中很重要，因为IL-33在上皮中特异性表达的缺失减轻了皮肤炎症。值得注意的是，即使在致敏后阻断IL-33， TLSP +抗原致敏后腹泻的发展也得到了改善。因此，IL-33在早期皮肤炎症和应激过程中发挥重要作用。这些数据揭示了IL-33在导致特应性皮炎到胃肠道过敏的“特应性行军”中的关键作用。
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 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 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, since 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 plays 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 atopic dermatitis to gastrointestinal allergy.