Thymic stromal lymphopoietin-mediated epicutaneous inflammation promotes acute diarrhea and anaphylaxis
Thymic stromal lymphopoietin-mediated epicutaneous inflammation promotes acute diarrhea and anaphylaxis
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DOI：
10.1172/jci77798
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发表时间：
2014-12-01
影响因子：
15.9
通讯作者：
Ziegler, Steven F.
中科院分区：
文献类型：
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作者：
Han, Hongwei;Thelen, Tennille D.;Ziegler, Steven F.
特应性皮炎(AD)与食物过敏密切相关；然而，引导AD进展到其他粘膜表面，包括胃肠道的过敏性炎症反应的机制尚不清楚。在这里，我们确定了用胸腺基质淋巴生成素(TSLP)和抗原表面致敏的小鼠暴露于重复口服相同抗原剂量会导致急性腹泻和过敏反应。在这个模型中，树突状细胞特异性的TSLP信号的丢失导致了由于缺乏敏感度而导致的过敏性腹泻的丢失。虽然口服变应原攻击时不需要TSLP反应，但需要CD4(+)T细胞，并在被引入幼稚宿主时传播疾病。此外，在皮肤致敏之前口服抗原可阻止过敏性疾病的发生。最后，缺乏IL-25受体的小鼠未能出现急性腹泻和过敏反应，突显了IL-25在启动肠道2型免疫中的作用。这些结果证明了TSLP和IL-25在特应性皮肤致敏到食物过敏反应过程中的作用，并为潜在的治疗干预措施的产生提供了一个模型系统。
Atopic dermatitis (AD) and food allergy are closely linked; however, the mechanisms that guide the progression of AD to allergic inflammatory responses at other mucosal surfaces, including the gastrointestinal tract, are not well understood. Here, we determined that exposure of mice that have been epicutaneously sensitized with thymic stromal lymphopoietin (TSLP) and antigen to repeated Oral doses of the same antigen induced acute diarrhea and anaphylaxis. In this model, loss of TSLP signaling specifically in DCs led to loss of induced allergic diarrhea through lack of sensitization. While TSLP responses were not required during oral allergen challenge, CD4(+)T cells were required and transferred disease when introduced into naive hosts. In addition, oral exposure to the antigen prior to skin sensitization blocked development of allergic disease. Finally, mice lacking the receptor for IL-25 failed to develop acute diarrhea and anaphylaxis, highlighting a role for IL-25 in the initiation of type 2 immunity in the intestine. These results demonstrate a role for TSLP and IL-25 in the atopic march from skin sensitization to food allergic responses and provide a model system for the generation of potential therapeutic interventions.