Atopic diseases, including atopic dermatitis (AD) and asthma, affect a large proportion of the population, with increasing prevalence worldwide. AD often precedes the development of asthma, known as the atopic march. Allergen sensitization developed through the barrier-defective skin of AD has been recognized to be a critical step leading to asthma, in which thymic stromal lymphopoietin (TSLP) was previously shown to be critical. In this study, using a laser-assistant microporation system to disrupt targeted skin layers for generating micropores at a precise anatomic depth of mouse skin, we model allergen exposure superficially or deeply in the skin, leading to epicutaneous sensitization or dermacutaneous sensitization that is associated with a different cytokine microenvironment. Our work shows a differential requirement for TSLP in these two contexts, and identifies an important function for IL-1β, which is independent of TSLP, in promoting allergen sensitization and subsequent allergic asthma.

特应性疾病，包括特应性皮炎 (AD) 和哮喘，影响着很大一部分人口，并且在世界范围内的患病率越来越高。AD 通常先于哮喘的发展，称为特应性进行曲。通过 AD 的屏障缺陷皮肤产生的过敏原致敏已被认为是导致哮喘的关键步骤，其中胸腺基质淋巴细胞生成素 (TSLP) 先前已被证明是关键的。在这项研究中，我们使用激光辅助微孔系统破坏目标皮肤层以在小鼠皮肤的精确解剖深度处产生微孔，我们模拟了皮肤表面或深层的过敏原暴露，导致表皮致敏或与皮肤相关的皮肤致敏不同的细胞因子微环境。